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Sample records for 4-5 times greater

  1. 4.5 Gbps high-speed real-time physical random bit generator.

    PubMed

    Wang, Anbang; Li, Pu; Zhang, Jianguo; Zhang, Jianzhong; Li, Lei; Wang, Yuncai

    2013-08-26

    We report a prototype of high-speed real-time physical random bit generator based on a chaotic laser. The chaotic laser consists of a semiconductor laser with optical feedback in fiber external cavity configuration. The chaotic laser intensity signal is quantized into binary stream by differential comparison which makes the amplitude distribution symmetric with respect to zero mean value. An exclusive-OR gate operation between two raw binary streams from the chaotic signal and its delayed signal is used to overcome the influences of the weak periodicity induced by the external cavity resonance inherent in the chaotic laser. After exclusive-OR operation, the prototype can generate a single fast random bit stream in real time without any off-line processing procedures. Its bit rate can be handily and continuously tuned up to 4.5 Gbps by a trigger clock. Experiment results demonstrate that our generator possesses high-quality randomness with verified by the three-standard-deviation criterion and industry-benchmark statistical tests.

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

    PubMed

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

    2012-10-01

    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(n)) measurements from below 10(9) (DD) to nearly 10(15) (DT). The detectors initially demonstrated detector-to-detector Y(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(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. 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.

  4. 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

  5. Coping Skills Help Explain How Future-Oriented Adolescents Accrue Greater Well-Being Over Time.

    PubMed

    Chua, Li Wen; Milfont, Taciano L; Jose, Paul E

    2015-11-01

    Adolescents who endorse greater levels of future orientation report greater well-being over time, but we do not know the mechanism by which this happens. The present longitudinal study examined whether both adaptive as well as maladaptive coping strategies might explain how future orientation leads to ill-being and well-being over time in young New Zealanders. A sample of 1,774 preadolescents and early adolescents (51.9 % female) aged 10-15 years at Time 1 completed a self-report survey three times with 1 year intervals in between. Longitudinal mediation path models were constructed to determine whether and how maladaptive and adaptive coping strategies at Time 2 functioned as mediators between future orientation at Time 1 and ill-being and well-being at Time 3. Results showed that future orientation predicted lower maladaptive coping, which in turn predicted lower substance use and self-harming behavior. All three well-being outcomes (i.e., happiness with weight, vitality, and sleep) were consistently predicted by future orientation, and all three pathways were mediated by both lower maladaptive and higher adaptive coping strategies (with the exception of happiness with weight, which was mediated only by lower maladaptive coping). The results suggest that several pathways by which future orientation leads to greater well-being occurs through an increased use of adaptive coping, a decreased use of maladaptive coping, or both.

  6. Time use differences in activity participation among children 4-5 years old with and without the risk of developing conduct problems.

    PubMed

    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 children at risk of developing conduct problems have different activity patterns compared to those not at risk. Specifically aspects of time use which concern involvement in activities that provide physical exertion, structure, rest and social engagement were examined. Data for this investigation were drawn from the Longitudinal Study of Australian Children (Wave 1) and focused on 4936 children aged 4-5 years. Findings indicate that children at risk of developing conduct problems spend significantly more time in: physical activities such as "riding a bike", and "in the company of adults only" than children not at risk of developing conduct problems but less time "with peers under adult supervision". Gender differences were also found in the same activities with boys participating in more "bike riding" and activities "without peers under adult supervision" than girls. Young children generally participated in more physical activities and spend more time "with peers while supervised by adults" on weekend days, and more time in "structured activities" and "in the company of adults only" on weekdays. These findings are discussed in respect of the potentially risky nature of physical activity choice and the contribution of adult supervision in the context of peer group participation for children at risk of developing conduct problems.

  7. Time of fusion of greater cornu with body of hyoid bone in Northwest Indians.

    PubMed

    Harjeet, Kaur; Synghal, Sanjeev; Kaur, Gagandeep; Aggarwal, Anjali; Wahee, Pratima

    2010-09-01

    Time of fusion of hyoid is of considerable interest for forensic experts in estimating the age of an individual when unrecognized decomposed bodies or skeletal remains are available. The present investigation was carried out to study the age of fusion in 200 hyoid bones (133 males and 67 females) varying in age from 18 to 85years. Fusion of greater cornu with the body of the hyoid bone was not seen till the age of 25years in both sexes. In the males complete fusion was seen in 22(16.5%) bilaterally and 16(6.0%) unilaterally while in females it was observed in 18(26.9%) bilaterally and 10(7.5%) unilaterally. No significant sexual and side differences were found between the incidence of fusion of greater cornu with the body of hyoid in almost all the age groups except in the last age group (61 & above) where the sexual difference was highly significant (p<0.001) in unilateral complete fusion and in total cases in bilateral complete fusion (p<0.01). The lesser cornu was not fused with the junction or with greater cornu till the age of 35years in males and 40years in females. The maximum incidence of fusion of lesser cornu was observed in last age group of 61years and above (55.6% males and 66.7% females). In conclusion estimation of age by using hyoid bone is not reliable as time of fusion of greater cornu with the body of hyoid is irregular. Subjects above the age of 60 years had either unilateral (13.2%) or bilateral (42.1%) nonfusion or also fusion (21.1% bilateral, 13.2% unilateral). The present method can be a supplementary approach for estimating age when the other skeletal remains are not available. PMID:20630786

  8. 43 CFR 4150.4-5 - Sale.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Sale. 4150.4-5 Section 4150.4-5 Public... Grazing Use § 4150.4-5 Sale. If the livestock are not redeemed on or before the date and time fixed for their sale, they shall be offered at public sale to the highest bidder by the authorized officer...

  9. 43 CFR 4150.4-5 - Sale.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Sale. 4150.4-5 Section 4150.4-5 Public... Grazing Use § 4150.4-5 Sale. If the livestock are not redeemed on or before the date and time fixed for their sale, they shall be offered at public sale to the highest bidder by the authorized officer...

  10. 43 CFR 4150.4-5 - Sale.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Sale. 4150.4-5 Section 4150.4-5 Public... Grazing Use § 4150.4-5 Sale. If the livestock are not redeemed on or before the date and time fixed for their sale, they shall be offered at public sale to the highest bidder by the authorized officer...

  11. 43 CFR 4150.4-5 - Sale.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Sale. 4150.4-5 Section 4150.4-5 Public... Grazing Use § 4150.4-5 Sale. If the livestock are not redeemed on or before the date and time fixed for their sale, they shall be offered at public sale to the highest bidder by the authorized officer...

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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…

  18. 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…

  19. 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…

  20. Does Social Connectedness Promote a Greater Sense of Well-Being in Adolescence over Time?

    ERIC Educational Resources Information Center

    Jose, Paul E.; Ryan, Nicholas; Pryor, Jan

    2012-01-01

    This longitudinal study was designed to investigate whether or not social connectedness predicts psychological well-being over time. Structural equation modeling was used to examine the temporal relations between these constructs assessed yearly for 3 years for a sample of 1,774 10- to 15-year-olds (at Time 1). Results indicated that global…

  1. 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

  2. Prolonged time to pregnancy is associated with a greater risk of adverse outcomes.

    PubMed

    Raatikainen, Kaisa; Harju, Maija; Hippeläinen, Maritta; Heinonen, Seppo

    2010-08-01

    Births with known time to pregnancy (TTP) during the period 1989-2007 (n=17,114) were analyzed to investigate associations between TTP and pregnancy outcome among couples that conceived spontaneously. The adjusted odds ratio (95% confidence interval) for poor neonatal health, including low Apgar score, low umbilical vein pH, and need for neonatal intensive care, was 1.51 (1.09-2.09) in women who had a TTP of 25-36 months and 1.60 (1.18-2.19) in women who had a TTP of >or=37 months compared with women with a TTP of 0-6 months.

  3. 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

  4. Time-dependent neuromuscular parameters in the plantar flexors support greater fatigability of old compared with younger males.

    PubMed

    Wallace, Jonathan W; Power, Geoffrey A; Rice, Charles L; Dalton, Brian H

    2016-02-01

    Older adults are more fatigable than young during dynamic tasks, especially those that involve moderate to fast unconstrained velocity shortening contractions. Rate of torque development (RTD), rate of velocity development (RVD) and rate of neuromuscular activation are time-dependent neuromuscular parameters which have not been explored in relation to age-related differences in fatigability. The purpose was to determine whether these time-dependent measures affect the greater age-related fatigability in peak power during moderately fast and maximal effort shortening plantar flexions. Neuromuscular properties were recorded from 10 old (~ 78 years) and 10 young (~ 24 years) men during 50 maximal-effort unconstrained velocity shortening plantar flexions against a resistance equivalent to 20% maximal voluntary isometric contraction torque. At task termination, peak power, and angular velocity, and torque at peak power were decreased by 30, 18, and 16%, respectively, for the young (p < 0.05), and 46, 28, 30% for the old (p < 0.05) compared to pre-fatigue values with the old exhibiting greater reductions across all measures (p<0.05). Voluntary RVD and RTD decreased, respectively, by 24 and 26% in the young and by 47 and 40% in the old at task termination, with greater decrements in the old (p < 0.05). Rate of neuromuscular activation of the soleus decreased over time for both age groups (~ 47%; p < 0.05), but for the medial gastrocnemius (MG) only the old experienced significant decrements (46%) by task termination. All parameters were correlated strongly with the fatigue-related reduction in peak power (r = 0.81-0.94, p < 0.05), except for MG and soleus rates of neuromuscular activation (r = 0.25-0.30, p > 0.10). Fatigue-related declines in voluntary RTD and RVD were both moderately correlated with MG rate of neuromuscular activation (r = 0.51-0.52, p < 0.05), but exhibited a trend with soleus (r = 0.39-0.41, p = 0.07-0.09). Thus, time-dependent factors, RVD and RTD

  5. 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.

  6. Rapid gut transit time and slow fecal isoflavone disappearance phenotype are associated with greater genistein bioavailability in women.

    PubMed

    Zheng, Yan; Hu, Jiang; Murphy, Patricia A; Alekel, D Lee; Franke, Warren D; Hendrich, Suzanne

    2003-10-01

    The bioavailability of soybean isoflavones varies widely among individuals due to many factors, including activities of gut microflora. To characterize factors that affect fecal isoflavone disappearance phenotype and isoflavone bioavailability in women, 35 Asian and 33 Caucasian women, 18-43 y of age, provided fecal samples for anaerobic incubation with isoflavones in vitro at two times 5 mo apart (Phases I and II). Diet, physical activity and health history were investigated at these times. A single dose of soymilk powder [1.2 mg (4.57 micromol) total isoflavone/kg body] was given to all subjects with breakfast in phase II. Daidzein and genistein from fecal incubations, urine and fecal samples were measured by reverse-phase HPLC. Three significantly different daidzein and two genistein disappearance phenotypes were identified from fecal isoflavone incubations. More Asians than Caucasians were identified within the high daidzein disappearance phenotype. Caucasians and Asians differed significantly in daily intake of red meat (0.3 +/- 0.1 vs. 1.0 +/- 0.1 servings/d), dairy foods (2.9 +/- 0.2 vs. 1.2 +/- 0.2 servings/d) and insoluble dietary fiber (3.6 +/- 0.3 vs. 1.4 +/- 0.3 g). BMI, maximal oxygen uptake (VO(2 max)) and physical activity level were significantly greater in Caucasians than in Asians. Asian subjects of the low genistein disappearance phenotype had more rapid gut transit time (GTT) and greater isoflavone bioavailability as reflected in urinary genistein excretion than did Asians of the high genistein disappearance phenotype (GTT, 40 +/- 8 vs. 63 +/- 5 h; 11.0 +/- 2.7 vs. 4.0 +/- 1.7% of ingested genistein excreted in urine). Caucasians of both genistein disappearance phenotypes had longer GTT than did Asian subjects (84 +/- 5 vs. 56 +/- 6 h) and resembled Asians of the high genistein disappearance phenotype in genistein bioavailability. Relatively rapid GTT coupled with a low fecal isoflavone disappearance phenotype as occurred in Asian but not

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Low precipitation events in the European Greater Alpine Region and their space-time patterns in the past 210 years.

    NASA Astrophysics Data System (ADS)

    Haslinger, Klaus; Holawe, Franz; Blöschl, Günter

    2016-04-01

    In this study space-time patterns of low precipitation events in the Greater Alpine Region (GAR) of Europe are investigated. A long term gridded dataset of monthly precipitation sums spanning the last 210 years is used to assess abnormally dry states by applying a monthly percentile deceedence threshold. Furthermore, these anomalies are calculated for 1, 3, 6 and 12 months moving averages. Contiguous areas of grid points below the threshold are recorded in a lookup table in order to assess the dry anomalies on an event-based approach. The overall event severity is determined by the mean deviation from the threshold level and the area affected. With this approach we are able to show that the most severe dry anomalies take place in the 1860s, 1850s and 1940s, although there are some differences in the occurrence over time in summer and winter. Winter dry anomalies are more frequent in the 19th century, whereas in summer no clear patterns are perceptible. A spatial clustering analysis of the anomaly fields also reveals distinct patterns in space, clearly indicating the Main Alpine Crest as a major divide of dry anomalies from North to South. A joint consideration of detected dry anomaly events and their associated temperature anomalies shows that in winter of the late 19th and early 20th century dry conditions are more often accompanied by cold temperatures in contrast to the last 50 years where dry anomalies are associated with above average winter temperatures. In general dry summers are more likely warmer than the long term mean, but there is also a considerable number of dry events with negative temperature anomalies, particularly in the late 19th and early 20th century.

  13. 28 CFR 4.5 - Character endorsements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Character endorsements. 4.5 Section 4.5 Judicial Administration DEPARTMENT OF JUSTICE PROCEDURE GOVERNING APPLICATIONS FOR CERTIFICATES OF... reputation in his community or in his circle of business or social acquaintances. Each letter or other...

  14. 28 CFR 4.5 - Character endorsements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Character endorsements. 4.5 Section 4.5 Judicial Administration DEPARTMENT OF JUSTICE PROCEDURE GOVERNING APPLICATIONS FOR CERTIFICATES OF... reputation in his community or in his circle of business or social acquaintances. Each letter or other...

  15. 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.

    1996-05-29

    This paper describes a prototype for this EAS (real time) in the Bay area. Approach is pragmatic, attempting to establish a prototype system at a low cost and quickly. A real-time warning system can protect the public and mitigate earthquake damage. The proposed system is a distributed network of real-time strong-motion monitoring stations that telemetered data in real time to a central analysis facility which could transmit earthquake parameter information to an area before elastic wave energy arrived. Upgrades and issues that should be resolved before an operational EAS can be established, are listed.

  16. 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…

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

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

    USGS Publications Warehouse

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

    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.

  5. Synthesis of 2-vinyl-3,4,5-trichlorothiophene and 3,4,5-trichlorothenyl acrylates

    SciTech Connect

    Akopyan, A.N.; Saakyan, A.A.; Gavalyan, V.B.; Smbatyan, A.G.; Darbinyan, E.G.

    1988-12-20

    Preparative methods were developed for the production of 2-vinyl-3,4,5-trichlorothiophene from 2-chloromethyl-3,4,5-trichlorothiophene by the Wittig reaction of a two-phase system and by catalytic dehydration of 2-(/alpha/-hydroxyethyl)-3,4,5-trichlorothiophene. In reaction with an aqueous solution of formaldehyde in the two-phase water-chloroform system in the presence of sodium carbonate 3,4,5-trichloroenyltrihenylphosphonoium chloride gives vinylthiophene (I) with an almost quantitative yield (93-95%). The process takes place under mild conditions (40/degree/C) and without a specially added phase-transfer catalyst, since the role of latter is evidently played by the phosphonium salt itself. 2-(/alpha/-Hydroxylethyl)-3,4,5-trichlorothiophene is formed by the reduction of the ketone (III) with sodium borohydride in methanol at 40/degree/C with a yield of 87%. The dehydration of the alcohol takes place at 180-200/degree/C in the presence of potassium bisulfate. The methods developed for the production of 2-vinylthiophene can be recommended as preparative methods on account of their simplicity, mild conditions, and high yields.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

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

    PubMed

    Fedy, Bradley C; Doherty, Kevin E

    2011-04-01

    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.

  15. 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.

  16. Effects of oil pollution at Kuwait's Greater Al-Burgan oil field on the timing of morning emergence, basking and foraging behaviors by the sand lizard Acanthodactylus scutellatus.

    PubMed

    Al-Hashem, M Abdulla; Brain, P F; Omar, S Ahmad

    2008-02-15

    An attempt was made to study the effects of oil pollution in a desert location (the Greater Al-Burgan oil fields, an area damaged in the second Gulf War) in Kuwait on the behaviour of the Sand lizard A. scutellatus. Polluted sites with apparently different degrees of contamination (namely tar mat, soot and clear sites) were compared with control areas outside this region. Between 2002 and 2003, ten lizards (5 of each sex) on each polluted and each control site were observed in the field at a time of the year when they were highly active. Air, substrate and burrow temperatures were recorded and lizards were monitored for their morning emergence times, as well as their basking and foraging activities. The present study confirmed that the morning emergence times and the basking behavior varied in sand lizards among the different pollution site categories. Physical changes in the tar mat sites caused the substrate temperatures in these locations to rise more quickly in the morning in response to solar gain than was the case in the other sites. This gives lizards in these locations the opportunity to emerge earlier and to start eating more quickly, giving them an energetic advantage (perhaps, in turn, influencing their rates of growth and fecundity). The clear sites had the next earliest emergence and were the next hottest but it is difficult to account for this in terms of the physical characteristics of this site. The basking times were clearly shorter on the dark soot and tar mat sites that appeared to have higher solar gain than control or clear sites. There did not appear to be any obvious differences in foraging activity of lizards in the different locations. It appears that some aspects of simple behaviour in these lizards provides a reliable, noninvasive indices for assessing oil pollution in desert locations. The precise impact of these changes in these reptiles on their long-term viability needs to be evaluated.

  17. 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

  18. 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...

  19. 12 CFR 4.5 - District and field offices.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false District and field offices. 4.5 Section 4.5... EXAMINERS Organization and Functions § 4.5 District and field offices. (a) District offices. Each district... Dakota, Utah, Washington, Wyoming, and Guam. (b) Field offices and duty stations. Field offices and...

  20. 10 CFR 4.5 - Communications and reports.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Communications and reports. 4.5 Section 4.5 Energy NUCLEAR... FINANCIAL ASSISTANCE FROM THE COMMISSION General Provisions § 4.5 Communications and reports. Except as otherwise indicated, communications and reports relating to this part may be sent to the NRC by...

  1. 10 CFR 4.5 - Communications and reports.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Communications and reports. 4.5 Section 4.5 Energy NUCLEAR... FINANCIAL ASSISTANCE FROM THE COMMISSION General Provisions § 4.5 Communications and reports. Except as otherwise indicated, communications and reports relating to this part may be sent to the NRC by...

  2. 10 CFR 4.5 - Communications and reports.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Communications and reports. 4.5 Section 4.5 Energy NUCLEAR... FINANCIAL ASSISTANCE FROM THE COMMISSION General Provisions § 4.5 Communications and reports. Except as otherwise indicated, communications and reports relating to this part may be sent to the NRC by...

  3. 10 CFR 4.5 - Communications and reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Communications and reports. 4.5 Section 4.5 Energy NUCLEAR... FINANCIAL ASSISTANCE FROM THE COMMISSION General Provisions § 4.5 Communications and reports. Except as otherwise indicated, communications and reports relating to this part may be sent to the NRC by...

  4. 10 CFR 4.5 - Communications and reports.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Communications and reports. 4.5 Section 4.5 Energy NUCLEAR... FINANCIAL ASSISTANCE FROM THE COMMISSION General Provisions § 4.5 Communications and reports. Except as otherwise indicated, communications and reports relating to this part may be sent to the NRC by...

  5. Stimulation of the faecal excretion of 2,4,5,2',4',5'-hexachlorobiphenyl in rats by squalane.

    PubMed

    Richter, E; Schäfer, S G; Fichtl, B

    1983-06-01

    Faecal excretion of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) was followed for 19 weeks in rats fed a control diet, or a squalane-supplemented diet, for up to 17 weeks. In 3 d after a single oral dose of 8 mg/kg of 6-CB, 20% dose was excreted in faeces as unchanged 6-CB, which probably represents that not-absorbed. From day 4 to 133 only an additional 2-4% dose was excreted in faeces by control animals. Addition of 8% squalane to the diet 2, 6 and 15 weeks after dosing resulted in a five-fold increase of daily 6-CB excretion in faeces independent of the time of beginning the treatment. Total excretion of 6-CB in faeces from day 4 to 133 was 3.6, 6-7 and 9.3% dose after 4, 13 and 17 weeks of squalane treatment, respectively. No adverse effects of long-term squalane treatment on body-weight gain, feed efficiency and organ weights were observed. Plasma cholesterol and triglycerides were significantly lowered. Independent of the duration of treatment, the livers of rats fed the squalane-supplemented diet contained 40-50 micrograms/g squalane. Within the limits of detection no squalane could be found in lungs, kidneys, abdominal fat, spleen and blood. It is concluded that 6-CB elimination can be enhanced by oral treatment with squalane even a long time after uptake of the poison. As there was no alteration in the tissue distribution of 6-CB, the 6-CB excreted after squalane treatment probably originates from all tissues.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5... Officer, Federal Election Commission, 999 E Street, NW., Washington, DC 20463, and shall indicate...

  12. 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...

  13. Determination of mass changes in phosphatidylinositol 4,5-bisphosphate and evidence for agonist-stimulated metabolism of inositol 1,4,5-trisphosphate in airway smooth muscle.

    PubMed Central

    Chilvers, E R; Batty, I H; Challiss, R A; Barnes, P J; Nahorski, S R

    1991-01-01

    Stimulation of muscarinic receptors in bovine tracheal smooth muscle (BTSM) causes a sustained increase in muscle tone, but a transient increase in the second messenger Ins(1,4,5)P3. To examine whether this brief increase in Ins(1,4,5)P3 mass results from transient formation or is due to agonist-stimulation of Ins(1,4,5)P3 metabolism, we have studied the relationship between mass changes in PtdIns(4,5)P2 and Ins(1,4,5)P3 accumulation, and changes in [3H]InsP3, [3H]PtdIns, [3H]PtdInsP1 and [3H]PtdInsP2 in carbachol-stimulated myo-[3H]inositol-prelabelled BTSM slices. Carbachol (0.1 mM) caused a rapid transient increase in Ins(1,4,5)P3 concentration (basal, 12.9 +/- 0.8 pmol/mg of protein; 5 s carbachol treatment, 27.1 +/- 1.5 pmol/mg of protein), with values returning to basal levels by 30 s, but a sustained accumulation of total [3H]InsP3s, with [3H]Ins(1,3,4)P3 being the predominant isomer present at later time points. In contrast, PtdIns(4,5)P2 mass, determined by radioreceptor assay of Ins(1,4,5)P3 in desalted alkaline hydrolysates of acidified chloroform/methanol tissue extracts, declined rapidly (basal, 941 +/- 22 pmol/mg of protein; 120 s carbachol, 365 +/- 22 pmol/mg of protein; t1/2 14 s) and remained at this new steady-state level for at least 20 min in the continued presence of carbachol. Addition of 10 microM-atropine 2 min after carbachol caused a prompt return of PtdIns(4,5)P2 concentration to prestimulated values (t1/2 210 s). Ongoing resynthesis of PtdIns(4,5)P2 after carbachol stimulation was demonstrated in [3H]inositol-labelled tissue by observing a persistent increase in the specific radioactivity of [3H]PtdInsP2, shown to be exclusively [3H]PtdIns(4,5)P2, over a 10 min period. These findings strongly suggest the occurrence of persistent receptor-mediated increases in PtdIns(4,5)P2 hydrolysis and Ins(1,4,5)P3 formation which, in conjunction with the transient accumulation of Ins(1,4,5)P3 observed, provide evidence that regulation of the

  14. Maturational regulation of inositol 1,4,5-trisphosphate metabolism in rabbit airway smooth muscle.

    PubMed Central

    Rosenberg, S M; Berry, G T; Yandrasitz, J R; Grunstein, M M

    1991-01-01

    Airway reactivity has been shown to vary with age; however, the mechanism(s) underlying this process remain unidentified. To elucidate the role of ontogenetic changes in phosphoinositide-linked signal transduction, we examined whether age-related differences in tracheal smooth muscle (TSM) contractility to carbachol (CCh) are associated with developmental changes in the production and metabolism of the second messenger, inositol 1,4,5-trisphosphate (Ins (1,4,5)P3). In TSM segments isolated from 2-wk-old and adult rabbits, both the maximal isometric contractile force and sensitivity (i.e., -logED50) to CCh (10(-10)-10(-4) M) were significantly greater in the immature vs. adult tissues (P less than 0.001). Similarly, Ins(1,4,5)P3 accumulation elicited by either receptor-coupled stimulation with CCh (10(-10)-10(-4) M) or post-receptor-mediated guanine nucleotide binding protein activation of permeabilized TSM with GTP gamma S (100 microM) was also significantly enhanced in 2-wk-old vs. adult TSM. Measurement of the activities of the degradative enzymes for Ins(1,4,5)P3 demonstrated that: (a) mean +/- SE maximal Ins(1,4,5)P3 3'-kinase activity was significantly reduced in the immature vs. adult TSM (i.e., approximately 71.7 +/- 6.0 vs. 137.8 +/- 10.0 pmol/min per mg protein, respectively; P less than 0.005); (b) by contrast, maximal Ins(1,4,5)P3 5'-phosphatase activity was significantly increased in the immature vs. adult TSM (i.e., 27.9 +/- 1.2 vs. 15.6 +/- 1.5 nmol/min per mg protein, respectively; P less than 0.001); and (c) the Km values for Ins(1,4,5)P3 5'-phosphatase were 14- and 19-fold greater than those for Ins(1,4,5)P3 3'-kinase in the 2-wk-old and adult TSM, respectively. Collectively, the findings suggest that the age-related decrease in agonist-induced rabbit TSM contractility is associated with a diminution in Ins(1,4,5)P3 accumulation which is attributed, at least in part, to ontogenetic changes in the relative activities of the degradative enzymes for

  15. Smooth muscle length-dependent PI(4,5)P2 synthesis and paxillin tyrosine phosphorylation.

    PubMed

    Sul, D; Baron, C B; Broome, R; Coburn, R F

    2001-07-01

    We studied effects of increasing the length of porcine trachealis muscle on 5.5 microM carbachol (CCh)-evoked phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] synthesis and other parameters of phosphatidylinositol (PI) turnover. PI(4,5)P2 resynthesis rates in muscle held at 1.0 optimal length (L(o)), measured over the first 6 min of CCh stimulation, were 140 +/- 12 and 227 +/- 14% of values found in muscle held at 0.5 L(o) and in free-floating muscle, respectively. Time-dependent changes in cellular masses of PI(4,5)P2, PI, and phosphatidic acid, and PI resynthesis rates, were also altered by the muscle length at which contraction occurred. In free-floating muscle, CCh did not evoke increases in tyrosine-phosphorylated paxillin (PTyr-paxillin), an index of beta1-integrin signaling; however, there were progressive increases in PTyr-paxillin in muscle held at 0.5 and 1.0 L(o) during contraction, which correlated with increases in PI(4,5)P2 synthesis rates. These data indicate that PI(4,5)P2 synthesis rates and other parameters of CCh-stimulated inositol phospholipid turnover are muscle length-dependent and provide evidence that supports the hypothesis that length-dependent beta1-integrin signals may exert control on CCh-activated PI(4,5)P2 synthesis.

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

    SciTech Connect

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

    2011-03-15

    The hydrothermal self-assemblies of Pb{sup 2+}/Cd{sup 2+} salt, 4,5-dichlorophthalic acid (dcpha), N{sub 2}H{sub 4}.H{sub 2}O together with 1,10-phenanthroline.H{sub 2}O (phen) or 2,2'-bipyridine (bpy) generated two new monoacylhydrazidate-bridged 1-D chained coordination polymers [Pb{sub 2}(DCPTH){sub 4}(phen){sub 2}] 1 and [Cd{sub 3}(DCPTH){sub 2}(dcph){sub 2}(bpy){sub 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{sub 2}H{sub 4}.H{sub 2}O. 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. -- Graphical abstract: By applying the in situ acylation reaction between 4,5-diclorophthalic acid and N{sub 2}H{sub 4}.H{sub 2}O, two 4,5-dichlorophthalhydrazidate-bridged chained compounds [Pb{sub 2}(DCPTH){sub 4}(phen){sub 2}] and [Cd{sub 3}(DCPTH){sub 2}(dcph){sub 2}(bpy){sub 2}] (4,5-dichlorophthalhydrazidate=DCPTH, and dcph=4,5-dichlorophthalate) were hydrothermally synthesized. Display Omitted Research highlights: > In this article, we first reported the preparations and structural characterization of two examples of 4,5-dichlorophthalhydrazidate-bridged chained coordination polymers [Pb{sub 2}(DCPTH){sub 4}(phen){sub 2}] 1 and [Cd{sub 3}(DCPTH){sub 2}(dcph){sub 2}(bpy){sub 2}] 2. 4,5-dichlorophthalhydrazidate derived from the hydrothermal in situ acylation reactions between 4,5-dichlorophthalic acid and N{sub 2}H{sub 4}.H{sub 2}O. > In this article, a simple method to judge whether the polycarboxylic acid precursors have acylated into the acylhydrazidate ligands is

  17. The first 1-alkyl-3-perfluoroalkyl-4,5- dimethyl-1,2,4-triazolium salts.

    PubMed

    Xue, Hong; Twamley, Brendan; Shreeve, Jean'ne M

    2004-02-20

    Syntheses of quaternary 1-alkyl-3-perfluoroalkyl-4,5-dimethyl-1,2,4-triazolium iodides have led to a variety of new quaternary salts via metathesis reactions. 1,4,5-Trimethyl-3-trifluoro-methyl-1,2,4-triazolium iodide (6) with LiN(SO(2)CF(3))(2), KSO(3)CF(3), AgClO(4), AgBF(4); 1-(3-fluoropropyl)-3-trifluoromethyl-4,5-dimethyl-1,2,4-triazolium iodide (7) with LiN(SO(2)CF(3))(2); and 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium iodide (8) with LiN(SO(2)CF(3))(2), AgClO(4), AgBF(4) gave excellent yields of new thermally stable and relatively low melting quaternary salts. The structure of 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium tetrafluoroborate (11c) was confirmed by single-crystal X-ray analysis. Although the molecular weight of 11c (cation) is 3-fold greater than that of the 3-trifluoromethyl derivative 9d, its melting point is 32 degrees C lower.

  18. 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

  19. 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

  20. 2,2\\',4,4\\',5-Pentabromodiphenyl ether (BDE-99)

    Integrated Risk Information System (IRIS)

    2,2 ' , 4,4 ' , 5 - Pentabromodiphenyl ether ( BDE - 99 ) ; CASRN 60348 - 60 - 9 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

  1. 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:

  2. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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. 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... functions, or causing substantial harm to the competitive position of the person, firm, partnership... intelligence investigation, information furnished by a confidential source; (v) Would disclose techniques...

  4. 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... functions, or causing substantial harm to the competitive position of the person, firm, partnership... intelligence investigation, information furnished by a confidential source; (v) Would disclose techniques...

  5. 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... Public Contracts COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED 4-NONPROFIT AGENCIES § 51-4.5 Violations by nonprofit agencies. (a) Any alleged violations of these regulations by...

  6. 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…

  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. 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

  11. 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

  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. Vibration Free 4.5 K Sorption Cooler

    NASA Astrophysics Data System (ADS)

    Burger, J. F.; Holland, H. J.; Meijer, R. J.; Sirbi, A.; ter Brake, H. J. M.

    2008-03-01

    At the University of Twente, a breadboard 4.5 K sorption cooler was developed under ESA contract. It has no moving parts and, therefore, is essentially vibration-free. Moreover, it has the potential of a very long life. This cooler is a favorite option for missions such as ESA's Darwin mission, which is a future space interferometer consisting of a few free flying telescopes and a central beam combiner. Because of the optics involved, hardly any vibration can be tolerated. The cooler consists of a hydrogen stage cooling from 80 K to 14.5 K and a helium stage establishing 10 mW at 4.5 K. Both stages use micro-porous activated carbon as the adsorption material. The two cooler stages need 8 W of input power and are heat sunk at two passive radiators at temperatures of about 50 and 80 K. We developed and built a demonstrator of the helium stage. In the paper, the design, realization and tests of this demonstrator cooler are reviewed.

  14. 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.

  15. 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

  16. 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.

  17. PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels.

    PubMed

    Itsuki, Kyohei; Imai, Yuko; Hase, Hideharu; Okamura, Yasushi; Inoue, Ryuji; Mori, Masayuki X

    2014-02-01

    Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C-insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of total

  18. 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

  19. 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.

  20. 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.

  1. Phosphorylation of the rat Ins(1,4,5)P₃ receptor at T930 within the coupling domain decreases its affinity to Ins(1,4,5)P₃.

    PubMed

    Haun, Shirley; Sun, Lu; Hubrack, Satanay; Yule, David; Machaca, Khaled

    2012-01-01

    The Ins(1,4,5)P 3 receptor acts as a central hub for Ca ( 2+) signaling by integrating multiple signaling modalities into Ca ( 2+) release from intracellular stores downstream of G-protein and tyrosine kinase-coupled receptor stimulation. As such, the Ins(1,4,5)P 3 receptor plays fundamental roles in cellular physiology. The regulation of the Ins(1,4,5)P 3 receptor is complex and involves protein-protein interactions, post-translational modifications, allosteric modulation, and regulation of its sub-cellular distribution. Phosphorylation has been implicated in the sensitization of Ins(1,4,5)P 3-dependent Ca ( 2+) release observed during oocyte maturation. Here we investigate the role of phosphorylation at T-930, a residue phosphorylated specifically during meiosis. We show that a phosphomimetic mutation at T-930 of the rat Ins(1,4,5)P 3 receptor results in decreased Ins(1,4,5)P 3-dependent Ca ( 2+) release and lowers the Ins(1,4,5)P 3 binding affinity of the receptor. These data, coupled to the sensitization of Ins(1,4,5)P 3-dependent Ca ( 2+) release during meiosis, argue that phosphorylation within the coupling domain of the Ins(1,4,5)P 3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P 3 receptor function.

  2. Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes.

    PubMed

    Kurz, T; Wolf, R A; Corr, P B

    1993-03-01

    The cellular content of phosphatidic acid can increase in response to several agonists either by phosphorylation of diacylglycerol after phospholipase C-catalyzed hydrolysis of phospholipids or directly through activation of phospholipase D. Although previous findings indicated that the generation of phosphatidic acid was exclusively a means of regulation of the cellular concentration of diacylglycerol, more recent studies have indicated that phosphatidic acid may also directly regulate several cellular functions. Accordingly, the present study was performed to assess whether phosphatidic acid could stimulate cardiac phospholipase C in intact adult rabbit ventricular myocytes. The mass of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] was determined by a specific and sensitive binding protein assay and by direct mass measurement using anion exchange chromatography for separation of selected inositol phosphates and gas chromatography and mass spectrometry for quantification of inositol monophosphate (IP1), inositol bisphosphate (IP2), inositol trisphosphate (IP3), and inositol tetrakisphosphate (IP4). Phosphatidic acid (10(-9)-10(-6) M) elicited a rapid concentration-dependent increase in Ins (1,4,5)P3 accumulation, with the peak fourfold to fivefold increase at 30 seconds of stimulation; the concentration required for 50% of maximal stimulation was 4.4 x 10(-8) M. The time course of individual inositol phosphates indicated a successive increase in the mass of IP3, IP4, IP2, and IP1 in response to stimulation with phosphatidic acid. The production of Ins (1,4,5)P3 in response to phosphatidic acid was not altered in the absence of extracellular calcium or in the presence of extracellular EGTA (10(-3) M). Thus, these findings indicate that phosphatidic acid is a potent activator of inositol phosphate production in adult ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Molecular determinants of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding to transient receptor potential V1 (TRPV1) channels.

    PubMed

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

    2015-01-23

    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.

  4. 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

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

    PubMed

    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.

  6. 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

  7. 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.

  8. 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

  9. Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.

    PubMed

    Clark, R L; Pessolano, A A; Shen, T Y; Jacobus, D P; Jones, H; Lotti, V J; Flataker, L M

    1978-09-01

    In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the pain thresholds of both the inflamed and normal foot were elevated. This is not commonly observed with nonsteroidal antiinflammatory agents. The most active compounds were 1,3-dihydro-3[3,4-(methylenedioxy)phenyl]imidazo[4,5-b]pyridin-2-one (I-15) and its N-allyl (I-21) and N-isopropyl (I-121) derivatives. In the triazole series the 3-(2-fluoro- and 2,4-difluorophenyl)triazolo[4,5-b]pyridines (T-1 and T-8) were the best. The imidazole compounds were somewhat superior in analgesic activity to codeine and d-propoxyphene without showing any narcotic characteristics. Some of the compounds also possessed activity against carrageenan-induced foot edema in the rat, so these compounds represent a new class of nonnarcotic analgesic antiinflammatories, capable of producing a greater degree of analgesia than that obtainable with other nonsteroidal antiinflammatory agents.

  10. Effects of oxygen and oxidation on tensile behavior of V-(4-5)Cr(4-5)Ti alloys

    SciTech Connect

    Natesan, K.; Soppet, W.K.; Uz, M.

    1997-10-01

    Vanadium-base alloys are potential candidates for applications such as the first wall and other structural components of fusion reactors, but a good understanding of the oxidation behavior of the alloys intended for elevated-temperature use is essential. The authors conducted a systematic study to determine the effects of time and temperature of air exposure on the oxidation behavior and microstructure of V-4Cr-4Ti and V-5Cr-5Ti alloys. Uniaxial tensile tests were conducted at room temperature and at 500 C on preoxidized specimens of the alloys to examine the effects of oxidation time and oxygen migration on maximum engineering stress and uniform and total elongation. The effect of preexposure of the specimens to environments with varying oxygen partial pressures on the tensile properties of both alloys was investigated. Extensive microstructural analyses of the oxygen-exposed/tensile-tested specimens were conducted to evaluate the cracking propensity for the alloys. In addition, tensile-property data for the alloys were correlated with oxygen pressure in the exposure environment, test temperature, and exposure time.

  11. 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.

  12. 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.

  13. 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.

  14. 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

    2014-10-15

    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.

  15. 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

  16. 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.

  17. Effect of simulated gastrointestinal conditions on biofilm formation by Salmonella 1,4,[5],12:i:-.

    PubMed

    Seixas, R; Gabriel, M; Machado, J; Tavares, L; Bernardo, F; Oliveira, M

    2014-01-01

    Salmonella Typhimurium 1,4,[5],12:i:- is a major serovar responsible for human salmonellosis whose biofilm-forming ability, influenced by environmental conditions like those found in the gastrointestinal tract, is one of the main contributing factors to its ability to persist in the host and thus one of the main causes of chronic relapsing infections. Most studies to evaluate biofilm formation are performed in microtiter assays using standard media. However, no reports are available on the ability of this serovar to produce biofilm under in vitro simulated gastrointestinal conditions which better correlate with the environment found in the gastrointestinal tract. To address this, a modified biofilm assay simulating intestinal fluid was conceived to assess the biofilm formation of 133 Salmonella Typhimurium 1,4,[5],12:i:- isolates with and without agitation and at three different time points (24 h, 48 h, and 72 h). The results were then compared to the existing microtiter method using conventional biofilm growth medium (Mueller Hinton Broth). Statistical analysis revealed significant differences in the results obtained between the three protocols used. The simulated human intestinal environment impaired biofilm production demonstrating that conditions like pH, agitation or the presence of enzymes can influence biofilm production. Therefore, results from in vitro simulation of in vivo conditions may contribute to unravelling factors relating to biofilm formation and persistence in the context of the human host. PMID:25093197

  18. Effect of Simulated Gastrointestinal Conditions on Biofilm Formation by Salmonella 1,4,[5],12:i:-

    PubMed Central

    Seixas, R.; Gabriel, M.; Machado, J.; Tavares, L.; Bernardo, F.; Oliveira, M.

    2014-01-01

    Salmonella Typhimurium 1,4,[5],12:i:- is a major serovar responsible for human salmonellosis whose biofilm-forming ability, influenced by environmental conditions like those found in the gastrointestinal tract, is one of the main contributing factors to its ability to persist in the host and thus one of the main causes of chronic relapsing infections. Most studies to evaluate biofilm formation are performed in microtiter assays using standard media. However, no reports are available on the ability of this serovar to produce biofilm under in vitro simulated gastrointestinal conditions which better correlate with the environment found in the gastrointestinal tract. To address this, a modified biofilm assay simulating intestinal fluid was conceived to assess the biofilm formation of 133 Salmonella Typhimurium 1,4,[5],12:i:- isolates with and without agitation and at three different time points (24 h, 48 h, and 72 h). The results were then compared to the existing microtiter method using conventional biofilm growth medium (Mueller Hinton Broth). Statistical analysis revealed significant differences in the results obtained between the three protocols used. The simulated human intestinal environment impaired biofilm production demonstrating that conditions like pH, agitation or the presence of enzymes can influence biofilm production. Therefore, results from in vitro simulation of in vivo conditions may contribute to unravelling factors relating to biofilm formation and persistence in the context of the human host. PMID:25093197

  19. PI(4,5)P2-binding effector proteins for vesicle exocytosis

    PubMed Central

    Martin, Thomas F. J.

    2014-01-01

    PI(4,5)P2 participates directly in priming and possibly fusion steps of Ca2+-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P2 reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P2 domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P2 directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P2-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P2 effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P2, which promotes clustering, but an activating role for PI(4,5)P2 in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P2-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P2-binding proteins. PMID:25280637

  20. 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.

  1. 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

  2. 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.

  3. 2,4,5-Trichlorophenoxyacetic acid promotes somatic embryogenesis in the rose cultivar "Livin' Easy" (Rosa sp.).

    PubMed

    Estabrooks, Tammy; Browne, Robin; Dong, Zhongmin

    2007-02-01

    Somatic embryogenesis (SE) offers vast potential for the clonal propagation of high-value roses. However, some recalcitrant cultivars unresponsive to commonly employed SE-inducing agents and low induction rates currently hinder the commercialization of SE technology in rose. Rose SE technology requires improvement before it can be implemented as a production system on a commercial scale. In the present work, we assessed 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a synthetic auxin not previously tested in rose, for its effectiveness to induce SE in the rose cultivar "Livin' Easy" (Rosa sp.). We ran a parallel comparison to the commonly used 2,4-dichlorophenoxyacetic acid (2,4-D). We tested each auxin with two different basal media: Murashige and Skoog (MS) basal medium and woody plant medium (WPM). MS medium resulted in somatic embryo production, whereas WPM did not. 2,4,5-T induced SE over a greater concentration range than 2,4-D's and resulted in significantly greater embryo yields. 2,4,5-T at a concentration of 10 or 25 microM was better for embrygenic tissue initiation than 2,4,5-T at 5 microM. Further embryo development occurred when the tissue was transferred to plant growth regulator (PGR) free medium or media with 40% the original auxin concentration. However, the PGR-free medium resulted in a high percentage of abnormal embryos (32.31%) compared to the media containing auxins. Upon transfer to germination medium, somatic embryos successfully converted into plantlets at rates ranging from 33.3 to 95.2%, depending on treatment. Survival rates 3 months ex vitro averaged 14.0 and 55.6% for 2,4-D- and 2,4,5-T-derived plantlets, respectively. Recurrent SE was observed in 60.2% of the plantlets growing on germination medium. This study is the first report of SE in the commercially valuable rose cultivar 'Livin' Easy' (Rosa sp.) and a suitable methodology was developed for SE of this rose cultivar.

  4. 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

  5. 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.

  6. Flood of June 4-5, 2002, in the Maquoketa River Basin, east-central Iowa

    USGS Publications Warehouse

    Eash, David A.

    2004-01-01

    Severe flooding occurred on June 4-5, 2002, in the Maquoketa River Basin in Delaware, Dubuque, Jackson, and Jones Counties, following thunderstorm activity over east-central Iowa. The rain gage at Cascade, Iowa, recorded a 14-hour rainfall of 6.0 inches at noon on June 4. Radar indications estimated as much as 8 to 10 inches of rain fell in the upper-middle part of the Maquoketa River Basin. Peak discharges on the Maquoketa River at Monticello of 47,500 cubic feet per second (recurrence interval estimated to be greater than 500 years as computed using flood-estimation equations developed by the U.S. Geological Survey), and at the Maquoketa River near Maquoketa streamflow-gaging station of 47,900 cubic feet per second (recurrence interval about 50 years), were determined for the flood. The peak discharge of the 2002 flood is nearly equal that of the 1944 flood (48,000 cubic feet per second), the largest flood on record in the Maquoketa River Basin. The 2002 flood is the largest known flood in the North Fork Maquoketa River Basin. A peak discharge of 22,600 cubic feet per second (recurrence interval about 110 years) was determined for the flood at the North Fork Maquoketa River near Fulton gaging station. Information about the basin and flood history, the 2002 thunderstorms and associated flooding, and a profile of high-water marks are presented for selected reaches along the Maquoketa and North Fork Maquoketa Rivers.

  7. Facilitation of the responses to injections of inositol 1,4,5-trisphosphate analogs in Limulus ventral photoreceptors.

    PubMed Central

    Levitan, I; Payne, R; Potter, B V; Hillman, P

    1994-01-01

    Injection of inositol 1,4,5-trisphosphate and its metabolically resistant analogs InsP3S3 and L-chiro-2,3,5-InsP3 into the ventral photoreceptors of Limulus results in the release of calcium from internal stores and in a current flow into the cells. We show here that the dependence of the current response on the amount of analog injected is supralinear. The injections also facilitate the responses to subsequent injections. We analyze the kinetics of the responses either by very slow application of the analogs directly into the lobe that is sensitive to InsP3 and light or by delivering a pulse into the nonsensitive lobe of the cell, in both cases creating a ramp of rising concentration in the sensitive region. Typically, a long latent period was followed by a strong brief inward current. The ratio between the latency and the duration of the response, defined as twice the time from half-amplitude to the peak of the response, reaches values greater than 10. Our analysis shows that this value cannot be attained within realistic models whose only nonlinearity is the cooperative binding of the ligand to its receptor. The observed ratio, however, can be achieved with a positive feedback model. Treatments that lead to partial depletion of calcium stores reversibly increase the latency of the response. We conclude that the mechanisms of the response of Limulus ventral eye to the metabolically resistant analogs of InsP3 probably involves a positive feedback mechanism and that the carrier of the feedback is likely to be Ca2+. PMID:7811929

  8. NMR investigation of the binding between human profilin I and inositol 1,4,5-triphosphate, the soluble headgroup of phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Richer, Sarah M; Stewart, Nichole K; Tomaszewski, John W; Stone, Martin J; Oakley, Martha G

    2008-12-23

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) is involved in the regulation of the actin cytoskeleton through interactions with a number of actin-binding proteins. We present here NMR titration experiments that monitor the interaction between the cytoskeletal protein profilin and inositol 1,4,5-triphosphate (IP(3)), the headgroup of PI(4,5)P(2). These experiments probe the interaction directly, at equilibrium, and with profilin in its native state. We show the binding between profilin and IP(3) can readily be observed at high concentrations, even though profilin does not bind to IP(3) under physiological conditions. Moreover, the titration data using wild-type profilin and an R88L mutant support the existence of at least three headgroup binding sites on profilin, consistent with previous experimentation with intact PI(4,5)P(2). This work suggests that various soluble inositol ligands can serve as effective probes to facilitate in vitro studies of PI-binding proteins that require membrane surfaces for high-affinity binding.

  9. [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

  10. Planning for greater confinement disposal

    SciTech Connect

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1985-01-01

    A report that provides guidance for planning for greater-confinement disposal (GCD) of low-level radioactive waste is being prepared. The report addresses procedures for selecting a GCD technology and provides information for implementing these procedures. The focus is on GCD; planning aspects common to GCD and shallow-land burial are covered by reference. Planning procedure topics covered include regulatory requirements, waste characterization, benefit-cost-risk assessment and pathway analysis methodologies, determination of need, waste-acceptance criteria, performance objectives, and comparative assessment of attributes that support these objectives. The major technologies covered include augered shafts, deep trenches, engineered structures, hydrofracture, improved waste forms, and high-integrity containers. Descriptive information is provided, and attributes that are relevant for risk assessment and operational requirements are given. 10 refs., 3 figs., 2 tabs.

  11. 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/.

  12. Coordination chemistry and applications of versatile 4,5-diazafluorene derivatives.

    PubMed

    Annibale, Vincent T; Song, Datong

    2016-01-01

    This perspective review will examine the coordination chemistry and applications of metal complexes of 4,5-diazafluorene derivatives. The versatile derivatives of 4,5-diazafluorene can serve multiple roles, and display a number of coordination modes. The ambidentate derivatives with multiple coordination sites can allow for the syntheses of coordination polymers, multimetallic, and macrocyclic complexes. In addition, certain 4,5-diazafluorene derivatives can serve as spectator ligands to support reactivity at the metal centre, or as reactive actor ligands engaging in atypical reactivity patterns. The applications of metal complexes of 4,5-diazafluorene derivatives in catalysis, photochemistry and photophysics, as well as in bioinorganic chemistry are also surveyed.

  13. 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

  14. 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

  15. Early Number and Arithmetic Performance of Ecuadorian 4-5-Year-Olds

    ERIC Educational Resources Information Center

    Bojorque, Gina; Torbeyns, Joke; Moscoso, Jheni; Van Nijlen, Daniël; Verschaffel, Lieven

    2015-01-01

    This study aimed at (a) constructing a reliable and valid test to assess Ecuadorian 4-5-year olds' number and arithmetic skills; (b) providing empirical data on Ecuadorian 4-5-year olds' number and arithmetic skills; and (c) confronting these children's actual performances with the performances expected by national experts in this domain. We…

  16. 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...

  17. 44 CFR 4.5 - What is the Administrator's obligation with respect to Federal interagency coordination?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true What is the Administrator's obligation with respect to Federal interagency coordination? 4.5 Section 4.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL...

  18. 44 CFR 4.5 - What is the Administrator's obligation with respect to Federal interagency coordination?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false What is the Administrator's obligation with respect to Federal interagency coordination? 4.5 Section 4.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL...

  19. 44 CFR 4.5 - What is the Administrator's obligation with respect to Federal interagency coordination?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false What is the Administrator's obligation with respect to Federal interagency coordination? 4.5 Section 4.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL...

  20. 44 CFR 4.5 - What is the Administrator's obligation with respect to Federal interagency coordination?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false What is the Administrator's obligation with respect to Federal interagency coordination? 4.5 Section 4.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL...

  1. 44 CFR 4.5 - What is the Administrator's obligation with respect to Federal interagency coordination?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false What is the Administrator's obligation with respect to Federal interagency coordination? 4.5 Section 4.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL...

  2. 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

  3. [Raoultella planticola, a new strain degrading 2,4,5-trichlorophenoxyacetic acid].

    PubMed

    Zharikova, N V; Markusheva, T V; Galkin, E G; Korobov, V V; Zhurenko, E Iu; Sitdikova, L R; Kolganova, T V; Kuznetsov, B B; Turova, T P

    2006-01-01

    A new strain that degrades the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) was isolated from soil, which was exposed to factors related to the petrochemical industry. According to its physiological, biochemical, cultural, and morphological traits, together with the sequence of the 16S rRNA gene, the strain was identified as Raoultella planticola 33-4ch. The strain could consume 2,4,5-T as a sole source of carbon and energy. The amount of 2,4,5-T in the culture medium decreased by 51% after five days of incubation. Raoultella planticola 33-4ch consumes 2,4,5-T to produce 4-chlorophenoxyacetic, phenoxyacetic, and 3-methyl-2,6-dioxo-4-hexenoic acids.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Timing and conditions of metamorphism and melt crystallization in Greater Himalayan rocks, eastern and central Bhutan: insight from U-Pb zircon and monazite geochronology and trace-element analyses

    NASA Astrophysics Data System (ADS)

    Zeiger, K.; Gordon, S. M.; Long, S. P.; Kylander-Clark, A. R. C.; Agustsson, K.; Penfold, M.

    2015-05-01

    Within the eastern Himalaya in central and eastern Bhutan, Greater Himalayan (GH) rocks are interpreted to have been thickened by the Kakhtang thrust (KT). In order to understand the metamorphic and exhumation history of the GH and to evaluate the structural significance of the KT, zircon and monazite from twenty samples were analyzed by laser-ablation split-stream ICPMS. In eastern Bhutan, zircon and monazite from samples collected in the KT hanging wall revealed ca. 36-28 Ma metamorphism. Subsequently, the initiation of melt crystallization shows a trend with structural distance above the KT, with early melt crystallization (ca. 27 Ma) in the structurally highest samples and younger melt crystallization (ca. 16 Ma) for leucosomes within the KT zone. Melt crystallization was protracted and continued until ca. 14-13 Ma in both the KT hanging wall and the footwall. In comparison, in central Bhutan, two leucosomes revealed extended melt crystallization from ca. 31 to 19 Ma. The youngest zircon dates from samples exposed structurally above and below the KT are similar, indicating that the KT was not as significant of a structure as other fault systems to which it has been correlated. However, the younging trend in the initiation of melt crystallization with decreasing structural distance above the KT argues that progressive underplating of ductile material assisted in the initial emplacement of the GH unit in central and eastern Bhutan. The KT likely represents a minor shear zone that aided in this underplating process.

  9. Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate.

    PubMed Central

    Galione, A; Swann, K; Georgiou, P; Whitaker, M

    1994-01-01

    1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. 2. A single injection of InsP3 gave a single HR above a threshold value of 0.3 nM. At 5 nM and above, InsP3 induced HRs with no detectable latency. At concentrations between these two values a latency was observed. The amplitude of the HR was independent of InsP3 concentration. 3. A second HR could be elicited by injection of InsP3, but five times more InsP3 was required to trigger a second HR, and 10-100 times more to give an HR of similar magnitude to the first, and there was no latency. 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). The initiation of an HR coincided with the second component of the [Ca2+]i increase. 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. 7. InsP3 can induce regenerative, all-or-none [Ca2+]i increase (CICR) in hamster eggs, often with a long latency, as well as non-regenerative increases. InsP3 injections desensitize CICR and cannot mimic all the features of Ca2+ signalling at fertilization in the hamster egg, in

  10. CRAC channel is inhibited by neomycin in a Ptdlns(4,5)P2-independent manner.

    PubMed

    Huang, Kun; Wang, Xuemei; Liu, Yanjun; Zhao, Yi

    2015-03-01

    Depletion of intracellular Ca(2+) stores evokes store-operated Ca(2+) entry through the Ca(2+) release-activated Ca(2+) (CRAC) channels. In this study, we found that the store-operated Ca(2+) entry was inhibited by neomycin, an aminoglycoside that strongly binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Patch clamp recordings revealed that neomycin blocked the CRAC currents reconstituted by co-expression of Orai1 and Stim1 in HEK293 cells. Using a rapamycin-inducible PtdIns(4,5)P2-specific phosphatase (Inp54p) system to manipulate the PtdIns(4,5)P2 in the plasma membrane, we found that the CRAC current was not altered by PtdIns(4,5)P2 depletion. This result suggests that PtdIns(4,5)P2 is not required for CRAC channel activity, and thereby, neomycin inhibits CRAC channels in a manner that is independent of neomycin-PtdIns(4,5)P2 binding.

  11. 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.

  12. Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization.

    PubMed

    Zhang, Zheng; Okawa, Haruhisa; Wang, Yuanyuan; Liman, Emily R

    2005-11-25

    TRPM4 is a Ca(2+)-activated nonselective cation channel that regulates membrane potential in response to intracellular Ca(2+) signaling. In lymphocytes it plays an essential role in shaping the pattern of intracellular Ca(2+) oscillations that lead to cytokine secretion. To better understand its role in this and other physiological processes, we investigated mechanisms by which TRPM4 is regulated. TRPM4 was expressed in ChoK1 cells, and currents were measured in excised patches. Under these conditions, TRPM4 currents were activated by micromolar concentrations of cytoplasmic Ca(2+) and progressively desensitized. Here we show that desensitization can be explained by a loss of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) from the channels. Poly-l-lysine, a PI(4,5)P(2) scavenger, caused rapid desensitization, whereas MgATP, at concentrations that activate lipid kinases, promoted recovery of TRPM4 currents. Application of exogenous PI(4,5)P(2) to the intracellular surface of the patch restored the properties of TRPM4 currents. Our results suggest that PI(4,5)P(2) acts to uncouple channel opening from changes in the transmembrane potential, allowing current activation at physiological voltages. These data argue that hydrolysis of PI(4,5)P(2) underlies desensitization of TRPM4 and support the idea that PI(4,5)P(2) is a general regulator for the gating of TRPM ion channels. PMID:16186107

  13. Chemical accessibility of the 4.5S RNA in spinach chloroplast ribosomes.

    PubMed Central

    Kumagai, I; Bartsch, M; Subramanian, A R; Erdmann, V A

    1983-01-01

    We have examined the accessibility to diethylpyrocarbonate of spinach chloroplast 4.5S ribosomal RNA when free and when it is part of the ribosomal structure. The modifications in free 4.5S RNA were found mostly in single-stranded regions of the secondary structure model proposed in our previous paper (Kumagai, I. et al. (1982) J.B.C. 257, 12924-28): adenines at positions 17, 19, 33, 36, 54, 55, 60, 64, 68, 72, 77, 86 and 87 were identified as the reactive residues. On the other hand, in 4.5S RNA in 70S ribosomes or 50S subunits, adenine 33 was exclusively modified, and its reactivity was much higher than in free 4.5S RNA. This highly accessible A33 of spinach 4.5S RNA is located within a characteristic seven nucleotide sequence, which is found in the 4.5S rRNAs from spinach, tobacco and a fern but deleted in 4.5S RNAs from maize and wheat. Images PMID:6828382

  14. 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.

  15. Nuclear Ptdlns(3,4,5)P3 signaling: an ongoing story.

    PubMed

    Déléris, Paul; Gayral, Stéphanie; Breton-Douillon, Monique

    2006-06-01

    Phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P(3)) is linked to a variety of cellular functions, such as growth, cell survival, and differentiation. Ptdlns(3,4,5)P(3) is primarily synthesized by class I phosphoinositide 3-kinases and its hydrolysis by two 3-phosphoinositide 3-phosphatases, PTEN and SHIP proteins, leads to the production of two other second messengers, Ptdlns(4,5)P(2) and Ptdlns(3,4)P(2), respectively. Evidence accumulated over the last years strongly suggest that Ptdlns(3,4,5)P(3) is an important component of signaling pathway operating within the nucleus. Moreover, recent advances indicated that nuclear translocation of cell surface receptors could activate nuclear phosphoinositide 3-kinase suggesting a new mode of signal transduction. The aim of this review is intended to summarize the state of our knowledge on nuclear Ptdlns(3,4,5)P(3) and its metabolizing enzymes, and to highlight the emerging roles for intranuclear Ptdlns(3,4,5)P(3). PMID:16645993

  16. 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.

  17. Molecular target sizes of inositol 1,4,5-trisphosphate receptors in liver and cerebellum.

    PubMed Central

    Nunn, D L; Potter, B V; Taylor, C W

    1990-01-01

    Ins(1,4,5)P3 is the intracellular messenger that mediates the effects of many cell-surface receptors on intracellular Ca2+ stores. Although radioligand-binding studies have identified high-affinity Ins(1,4,5)P3-binding sites in many tissues, these have not yet been convincingly shown to be the receptors that mediate Ca2+ mobilization, nor is it clear whether there are differences in these binding sites between tissues. Here we report that Ins(1,4,5)P3 binds to a single class of high-affinity sites in both permeabilized hepatocytes (KD = 7.8 +/- 1.1 nM) and cerebellar membranes (KD = 6.5 +/- 2.4 nM), and provide evidence that these are unlikely to reflect binding to either of the enzymes known to metabolize Ins(1,4,5)P3. Furthermore, the rank order of potency of synthetic inositol phosphate analogues in displacing specifically bound Ins(1,4,5)P3 is the same as their rank order of potency in stimulating mobilization of intracellular Ca2+ stores, suggesting that the Ins(1,4,5)P3-binding site may be the physiological receptor. Radiation inactivation of the Ins(1,4,5)P3-binding sites of liver and cerebellum reveals that they have similar molecular target sizes: 257 +/- 36 kDa in liver and 258 +/- 20 kDa in cerebellum. We conclude that an Ins(1,4,5)P3-binding protein with a molecular target size of about 260 kDa is probably the receptor that mediates Ca2+ mobilization in hepatocytes, and our limited data provide no evidence to distinguish this from the cerebellar Ins(1,4,5)P3-binding protein. PMID:2154187

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Deflagellation of Chlamydomonas reinhardtii follows a rapid transitory accumulation of inositol 1,4,5-trisphosphate and requires Ca2+ entry

    PubMed Central

    1993-01-01

    C. reinhardtii sheds its flagella in response to acidification. Previously, we showed correlations between pH shock, deflagellation, and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production, but 100% of cells deflagellated by 5 s, which was the earliest that Ins(1,4,5)P3 accumulation could be accurately measured by techniques available to us at that time (Quarmby, L. M., Y. G. Yueh, J. L. Cheshire, L. R. Keller, W. J. Snell, and R. C. Crain. J. Cell Biol. 1992. 116:737-744). To learn about the causal relationship between Ins(1,4,5)P3 accumulation and deflagellation, we extended these studies to early times using a continuous-flow rapid-quench device. Within 1 s of acidification to pH 4.3-4.5, 100% of cells deflagellated. A transient peak of Ins(1,4,5)P3 was observed 250-350 ms after pH shock, preceding deflagellation. Preincubation with 10 microM neomycin, which prevents hydrolysis of phosphatidylinositol 4,5-bisphosphate, inhibited both the transient production of Ins(1,4,5)P3 and the subsequent deflagellation. The nonspecific Ca2+ channel blockers La3+ and Cd2+ prevented flagellar excision induced by mastoparan without inhibiting rapid Ins(1,4,5)P3 production. Likewise, the Ins(1,4,5)P3-gated channel inhibitors ruthenium red and heparin blocked deflagellation in response to mastoparan. These studies were extended to mutants defective in flagellar excision. Fa-1, a mutant defective in flagellar structure, produced Ins(1,4,5)P3 but failed to deflagellate. These results support a model in which acid pH activates a putative cellular receptor leading to G-protein dependent activation of phospholipase C and accumulation of Ins(1,4,5)P3. These events are upstream of Ins(1,4,5)P3-dependent Ca2+ entry from the medium, and of deflagellation. PMID:8227146

  4. c-Fos-activated synthesis of nuclear phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂] promotes global transcriptional changes.

    PubMed

    Ferrero, Gabriel O; Renner, Marianne L; Gil, Germán A; Rodríguez-Berdini, Lucia; Caputto, Beatriz L

    2014-08-01

    c-Fos is a well-recognized member of the AP-1 (activator protein-1) family of transcription factors. In addition to this canonical activity, we previously showed that cytoplasmic c-Fos activates phospholipid synthesis through a mechanism independent of its genomic AP-1 activity. c-Fos associates with particular enzymes of the lipid synthesis pathway at the endoplasmic reticulum and increases the Vmax of the reactions without modifying the Km values. This lipid synthesis activation is associated with events of differentiation and proliferation that require high rates of membrane biogenesis. Since lipid synthesis also occurs in the nucleus, and different phospholipids have been assigned transcription regulatory functions, in the present study we examine if c-Fos also acts as a regulator of phospholipid synthesis in the nucleus. Furthermore, we examine if c-Fos modulates transcription through its phospholipid synthesis activator capacity. We show that nuclear-localized c-Fos associates with and activates PI4P5K (phosphatidylinositol-4-monophosphate 5-kinase), but not with PI4KIIIβ (type IIIβ phosphatidylinositol 4-kinase) thus promoting PtdIns(4,5)P₂ (phosphatidylinositol 4,5-bisphosphate) formation, which, in turn, promotes transcriptional changes. We propose c-Fos as a key regulator of nuclear PtdIns(4,5)P₂ synthesis in response to growth signals that results in c-Fos-dependent transcriptional changes promoted by the newly synthesized lipids.

  5. 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

  6. Synthesis and structure-activity relationships of 2-alkylidenethiazolidine-4,5-diones as antibiotic agents.

    PubMed

    Albrecht, Uwe; Gördes, Dirk; Schmidt, Enrico; Thurow, Kerstin; Lalk, Michael; Langer, Peter

    2005-07-15

    2-Alkylidenethiazolidine-4,5-diones were prepared by novel one-pot cyclizations of arylacetonitriles with isothiocyanates and ethyl 2-chloro-2-oxoacetate. The products show antibiotic activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus.

  7. Inositol 1,4,5-trisphosphate mass changes from fertilization through first cleavage in Xenopus laevis.

    PubMed Central

    Stith, B J; Goalstone, M; Silva, S; Jaynes, C

    1993-01-01

    After fertilization in Xenopus laevis, inositol 1,4,5-trisphosphate (IP3) mass increased from 53 to 261 fmol/cell and returned to near basal by 10 min after insemination. IP3 was also elevated over control egg levels during first mitosis and first cleavage. Because IP3 levels and the fertilization calcium wave decline at about the same time and because calcium ionophore or pricking the egg increased IP3, the fertilization calcium wave may be due to calcium-induced IP3 production. In addition, the onset of sperm motility was associated with an increase, whereas the acrosomal reaction was accompanied by a decrease in IP3 mass. Combining our published data with this report, the first chronology of the levels of IP3 from the induction of meiosis (maturation) through fertilization and cleavage in one cellular system is summarized. These data suggest an in vivo dose response for IP3 and calcium release. A small (17 fmol/cell) IP3 change during the induction of meiosis may not be associated with a calcium change. Larger IP3 changes at cleavage (40 fmol/cell) and mitosis (125 fmol/cell) are associated with localized small calcium increases, whereas the largest IP3 change (208 fmol/cell) is associated with the large calcium increase at fertilization. PMID:8507898

  8. 3,3',4,4',5,5'-hexahydroxystilbene impairs melanoma progression in a metastatic mouse model.

    PubMed

    Paulitschke, Verena; Schicher, Nikolaus; Szekeres, Thomas; Jäger, Walter; Elbling, Leonilla; Riemer, Angelika B; Scheiner, Otto; Trimurtulu, Golakoti; Venkateswarlu, Somepalli; Mikula, Mario; Swoboda, Alexander; Fiebiger, Edda; Gerner, Christopher; Pehamberger, Hubert; Kunstfeld, Rainer

    2010-06-01

    Stilbenes comprise a group of polyphenolic compounds, which exert inhibitory effects on various malignancies. The aim of this study was to evaluate the antitumor effects of a previously unreported stilbene derivative-3,3',4,4',5,5'-hexahydroxystilbene, termed M8-on human melanoma cells. Cell-cycle analysis of the metastatic melanoma cell line M24met showed that M8 treatment induces G(2)/M arrest accompanied with a dose- and time-dependent upregulation of p21 and downregulation of CDK-2 and leads to apoptosis. M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. In addition, M8 inhibited cell migration in Matrigel assays. Shotgun proteomics and western analysis showed the regulation among others of paxillin, integrin-linked protein kinase, p21-activated kinase, and ROCK-1 indicating that M8 inhibits mesenchymal and amoeboid cell migration. These in vitro data were confirmed in vivo in a metastatic human melanoma severe combined immunodeficient (SCID) mouse model. We showed that M8 significantly impairs tumor growth. M8 also interfered with the metastatic process, as M8 treatment prevented the metastatic spread of melanoma cells to distant lymph nodes in vivo. In summary, M8 exerts strong antitumor effects with the potential to become a new drug for the treatment of metastatic melanoma.

  9. 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.

  10. Electron paramagnetic resonance study of 3,4,5-trimethoxytetraphenyl porphyrinoxovanadium (IV) complex.

    PubMed

    Sharma, Swati; Kumar, Anil; Chand, Prem; Sharma, B K; Sarkar, Sabyasachi

    2006-03-01

    3,4,5-Trimetoxytetraphenylporphyrinoxovanadium (IV) complex (3,4,5-TMVOTPP) was synthesized by a new one pot synthetic method. The complex was studied in the form of single crystal, powder (polycrystalline state), solution and frozen solution (glassy state) by electron paramagnetic resonance (EPR) between room temperature (RT) and liquid nitrogen temperature (LNT). Interestingly a well-resolved octet in the EPR spectrum at RT is observed in the pure paramagnetic state of the crystal. This observation is attributed to a greatly reduced dipolar interaction between paramagnetic vanadyl ions due to the large size of the molecule and the resultant stacking in the crystalline state. The line width of the EPR signals in single crystal at RT is approximately 3.3 mT which is more than the usual line width in diluted paramagnets ( approximately 1.5 mT) and is attributed to some kind of broadening effect akin to slow motion broadening. The line width in solvents is more than the crystal value but decreases appreciably at low temperatures. The decrease in line width at low temperature is attributed to the increase in spin-lattice-relaxation time and quenching of RT broadening motion. Only one octet is observed in the crystal EPR spectra which suggests only one formula unit per unit cell or a parallel/antiparallel ordering of V=O vectors in case the formula units per unit cell are more than one. This result needs verification by a detailed X-ray investigation. The crystalline field symmetry around the V(4+) metal ion is revealed to be axial by the observed angular dependence of the EPR spectrum and the powder EPR spectrum. No super hyperfine splitting of the hyperfine lines of the vanadyl ion is observed in solid state or diluted glass up to liquid nitrogen temperature. This suggests an expected weak in-plane pi-bonding with ligands. The spin Hamiltonian parameters for vanadyl ion in crystal, powder, diluted solutions and frozen glasses are evaluated and discussed.

  11. 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

  12. Phosphatidylinositol 4,5-bisphosphate-dependent regulation of the output in lobster olfactory receptor neurons.

    PubMed

    Bobkov, Yuriy V; Pezier, Adeline; Corey, Elizabeth A; Ache, Barry W

    2010-05-01

    Transient receptor potential (TRP) channels often play a role in sensory transduction, including chemosensory transduction. TRP channels, a common downstream target of phosphoinositide (PI) signaling, can be modulated by exogenous phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] and/or diacylglycerol (DAG). Lobster olfactory receptor neurons (ORNs) express a TRP-related, non-selective, calcium/magnesium-permeable, sodium/calcium-gated cation (SGC) channel. Here we report that PIs regulate the function of the calcium-activated form of the lobster channel. Sequestering of endogenous PI(4,5)P2, either with an anti-PI(4,5)P2 antibody or by electrostatic screening with polyvalent cations, blocks the channel. Exogenous PI(3,4,5)P3 activates the channel independently of intracellular sodium and/or calcium. Exogenous non-hydrolysable DAG analogs fail to change the gating parameters of the channel, suggesting the channel is insensitive to DAG. Electrophysiological recording from lobster ORNs in situ using a panel of pharmacological tools targeting the key components of both PI and DAG metabolism (phospholipase C, phosphoinositide 4-kinase and DAG kinase) extend these findings to the intact ORN. PI(4,5)P2 depletion suppresses both the odorant-evoked discharge and whole-cell current of the cells, and does so possibly independently of DAG production. Collectively, our results argue that PIs can regulate output in lobster ORNs, at least in part through their action on the lobster SGC channel.

  13. Evidence for an approximately 4.5 aeon age of plagioclase clasts in a lunar highland breccia

    NASA Technical Reports Server (NTRS)

    Jessberger, E. K.; Huneke, J. C.; Wasserburg, G. J.

    1974-01-01

    Argon from neutron-irradiated mineral separates and whole rock samples of a metamorphosed breccia (65015) from Apollo 16 has been analyzed with a large number of gas extraction steps in order to obtain a high resolution in the apparent ages and to identify the gas released from different sources. The results on plagioclase show a Ar-40/Ar-39 plateau age of 3.98 b.y. which is attributed to the time of metamorphism, and an age of about 4.5 b.y. in the high-temperature fraction. Correlation of the release pattern with Ar-37 instead of Ar-39 permits the association of the approximate 4.5 b.y. age with relict plagioclasts which were demonstrated in previous petrographic and Rb-Sr studies as being unequilibrated. This result suggests that it is possible to identify lithic components which represent the early lunar crust.

  14. 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.

  15. 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

  16. NT4/5 mutant mice have deficiency in gustatory papillae and taste bud formation.

    PubMed

    Liebl, D J; Mbiene, J P; Parada, L F

    1999-09-15

    Neurotrophins are key determinants for controlling the survival of peripheral neurons during development. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4/5) exert their action through a common trkB receptor but independently support gustatory sensory neurons. To assess the role of NT4/5 during development, we examined the postnatal development and maintenance of fungiform taste buds in mice carrying a deletion of NT4/5. The absence of NT4/5 results in embryonic deficits in gustatory innervation and a reduced number of fungiform papillae at birth. No degenerative deficits of fungiform papillae were observed for the first 3 weeks of postnatal development. However, these remaining fungiform papillae were smaller in appearance and many did not contain taste pores. By postnatal day 60, there was 63% decrease in the number of fungiform papillae, and remaining papillae were smaller in size or modified into filiform-like spines. These papillae had either no taste bud or a taste bud with a reduced number of taste cells compared to controls. These findings demonstrate that the NT4/5 gene functions in the maintenance of fungiform gustatory papillae and raises the possibility for an earlier role in development. PMID:10479455

  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. Susceptibility of greater sage-grouse to experimental infection with West Nile virus.

    PubMed

    Clark, Larry; Hall, Jeffrey; McLean, Robert; Dunbar, Michael; Klenk, Kaci; Bowen, Richard; Smeraski, Cynthia A

    2006-01-01

    Populations of greater sage-grouse (Centrocercus urophasianus) have declined 45-80% in North America since 1950. Although much of this decline has been attributed to habitat loss, recent field studies have indicated that West Nile virus (WNV) has had a significant negative impact on local populations of grouse. We confirm the susceptibility of greater sage-grouse to WNV infection in laboratory experimental studies. Grouse were challenged by subcutaneous injection of WNV (10(3.2) plaque-forming units [PFUs]). All grouse died within 6 days of infection. The Kaplan-Meier estimate for 50% survival was 4.5 days. Mean peak viremia for nonvaccinated birds was 10(6.4) PFUs/ml (+/-10(0.2) PFUs/ml, standard error of the mean [SEM]). Virus was shed cloacally and orally. Four of the five vaccinated grouse died, but survival time was increased (50% survival=9.5 days), with 1 grouse surviving to the end-point of the experiment (14 days) with no signs of illness. Mean peak viremia for the vaccinated birds was 10(2.3) PFUs/ml (+/-10(0.6) PFUs/ml, SEM). Two birds cleared the virus from their blood before death or euthanasia. These data emphasize the high susceptibility of greater sage-grouse to infection with WNV.

  19. In vivo formation and persistence of DNA and protein adducts in mouse and rat skin exposed to (+/-)benzo(a)pyrene-4,5-oxide

    SciTech Connect

    Rojas, M.; Alexandrov, K.

    1986-02-01

    The objective of the present study was to compare DNA and protein adduct formation of benzo(a)pyrene-4,5-oxide (BPO) in vivo and to determine the persistence of the adducts in both mouse and rat epidermis. (+/-)BPO at a dose of 100 nmol/mouse and 200 nmol/rat was topically applied to male Swiss mice and Wistar rats. Three hours after application, there was 3-fold less binding of BPO to mouse epidermal DNA than to rat epidermal DNA; inversely, the amount of BPO bound to mouse skin protein was 3.6 times higher than in rat skin protein. One and three weeks after application of BPO, persistence of 17-20% of the initial amount of BPO-DNA adducts and 2-4% of initial amount of BPO bound to protein was detected in both mouse and rat skin epidermis. H.p.l.c. analysis of the enzymatic hydrolysates of DNA from mouse and rat epidermis 3 h after application of BPO showed five distinct products: one early-eluting, two BPO-deoxyguanosine (dGuo) (ratio 1.5:1) and two BPO-deoxyadenosine (dAdo) adducts (ratio 2:1). The ratio of the total modified dGuo to the total modified dAdo was 2:1. The amount of total BPO-dGuo and BPO-dAdo adducts was 3.5 times greater in rat than in mouse epidermis. Persistence of the major BPO-dAdo adduct was observed in mouse and rat epidermal DNA, and 1 and 3 weeks after topical application of BPO there was a 6-fold greater amount of the persisting BPO-dAdo adduct in rat skin epidermis than in mouse skin epidermis (4.1 and 0.66 pmol/mg DNA, respectively). Minor amounts of the BPO-dGuo were found to persist in rat skin epidermis DNA.

  20. Suppression of male-specific cytochrome P450 2c and its mRNA by 3,4,5,3',4',5'-hexachlorobiphenyl in rat liver is not causally related to changes in serum testosterone.

    PubMed

    Yeowell, H N; Waxman, D J; LeBlanc, G A; Linko, P; Goldstein, J A

    1989-06-01

    Rat cytochrome P450 2c (P450 gene IIC11) is a constitutive, male-specific hepatic enzyme which is suppressed greater than 90% by treatment with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) [H. N. Yeowell et al. (1987) Mol. Pharmacol. 32, 340-347]. HCB also decreases serum testosterone levels in adult male rats (greater than 98% loss). The present study assesses whether the suppression of P450 2c by HCB is a direct result of its effects on serum testosterone levels. Further, the site along the hypothalamic-pituitary-testicular axis at which HCB acts to depress testosterone secretion was examined. Administration of the synthetic androgen methyltrienolone to HCB-treated rats failed to prevent the suppression of P450 2c mRNA and its associated microsomal steroid 16 alpha-hydroxylase activity under conditions where it effectively reversed the large decrease in P450 2c mRNA and steroid 16 alpha-hydroxylase activity produced by castration. Hepatic steroid 6 beta-hydroxylase activity, which is catalyzed primarily by P450 2a (P450 gene IIIA2), was also suppressed by HCB and was not protected by methyltrienolone. Administration of either human chorionic gonadotropin, an analog of pituitary-derived luteinizing hormone, or the hypothalamic luteinizing hormone releasing hormone elevated serum testosterone levels to a much smaller extent in HCB-treated rats than in control rats. These results indicate that the effects of HCB on serum testosterone levels reflect its effects on testicular function rather than the pituitary or hypothalamus. However, the present study demonstrates that the consequential reduction in serum testosterone levels in HCB-treated rats is not causally related to the reduction in hepatic P450 2c levels. Thus, HCB must also act on some other regulatory mechanism involved in the expression of this protein.

  1. A White Light Megaflare on the dM4.5e Star YZ CMi

    NASA Astrophysics Data System (ADS)

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

    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 Å 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 Å to 4800 Å 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~ 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 (~3-16 times) larger. These data will provide critical constraints for understanding the physics underlying the mysterious blue continuum radiation in stellar flares. Based on observations obtained with the Apache Point Observatory 3.5 m Telescope, which is owned and operated by the Astrophysical Research Consortium.

  2. 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.

  3. 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.

  4. 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.

  5. Compatibility study of trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin (TNAD) with some energetic components and inert materials.

    PubMed

    Yan, Qi-Long; Xiao-Jiang, Li; La-Ying, Zhang; Ji-Zhen, Li; Hong-Li, Li; Zi-Ru, Liu

    2008-12-30

    The compatibility of trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin (TNAD) with some energetic components and inert materials of solid propellants was studied by using the pressure DSC method where, cyclotetramethylenetetranitroamine (HMX), cyclotrimethylenetrinitramine (RDX), 1,4-dinitropiperazine (DNP), 1.25/1-NC/NG mixture, lead 3-nitro-1,2,4-triazol-5-onate (NTO-Pb), aluminum powder (Al, particle size=13.6microm) and N-nitrodihydroxyethylaminedinitrate (DINA) were used as energetic components and polyethylene glycol (PEG), polyoxytetramethylene-co-oxyethylene (PET), addition product of hexamethylene diisocyanate and water (N-100), 2-nitrodianiline (2-NDPA), 1,3-dimethyl-1,3-diphenyl urea (C2), carbon black (C.B.), aluminum oxide (Al2O3), cupric 2,4-dihydroxy-benzoate (beta-Cu), cupric adipate (AD-Cu) and lead phthalate (phi-Pb) were used as inert materials. It was concluded that the binary systems of TNAD with NTO-Pb, RDX, PET and Al powder are compatible, and systems of TNAD with DINA and HMX are slightly sensitive, and with 2-NDPA, phi-Pb, beta-Cu, AD-Cu and Al2O3 are sensitive, and with PEG, N-100, C2 and C.B. are incompatible. The impact and friction sensitivity data of the TNAD and TNAD in combination with the other energetic materials under present study was also obtained, and there was no consequential affiliation between sensitivity and compatibility.

  6. 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.

  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. 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.

  9. 3,4,5-Trichloroaniline nephrotoxicity in vitro: potential role of free radicals and renal biotransformation.

    PubMed

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

    2014-11-13

    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.

  10. 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

  11. Synthesis, antitumor, and antibacterial activity of bis[4,5-diarylimidazol-2-ylidene]methane derivatives.

    PubMed

    Liu, Wukun; Chen, Xiaohua; Gust, Ronald

    2012-07-01

    Cationic [bis(1,3-diethyl-4,5-diarylimidazol-2-ylidene)]Au(I) bromide complexes have demonstrated considerable potential as new antitumor agents. In order to investigate whether the gold is crucial for the antitumor activity, the imidazole ligands were connected by a methylene bridge. Biological evaluation revealed that bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]methane compounds exhibited growth inhibition effects against mammary (MCF-7 and MDA-MB 231) and colon (HT-29) carcinoma cell lines. In comparison with gold complexes, the methylene derivatives showed drastically reduced cell growth inhibitory properties. However, the growth of bacteria was significantly inhibited by bis[1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]methane dibromide (4) and opens a new application of this compound type.

  12. 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.

  13. Multisensor Arrays for Greater Reliability and Accuracy

    NASA Technical Reports Server (NTRS)

    Immer, Christopher; Eckhoff, Anthony; Lane, John; Perotti, Jose; Randazzo, John; Blalock, Norman; Ree, Jeff

    2004-01-01

    Arrays of multiple, nominally identical sensors with sensor-output-processing electronic hardware and software are being developed in order to obtain accuracy, reliability, and lifetime greater than those of single sensors. The conceptual basis of this development lies in the statistical behavior of multiple sensors and a multisensor-array (MSA) algorithm that exploits that behavior. In addition, advances in microelectromechanical systems (MEMS) and integrated circuits are exploited. A typical sensor unit according to this concept includes multiple MEMS sensors and sensor-readout circuitry fabricated together on a single chip and packaged compactly with a microprocessor that performs several functions, including execution of the MSA algorithm. In the MSA algorithm, the readings from all the sensors in an array at a given instant of time are compared and the reliability of each sensor is quantified. This comparison of readings and quantification of reliabilities involves the calculation of the ratio between every sensor reading and every other sensor reading, plus calculation of the sum of all such ratios. Then one output reading for the given instant of time is computed as a weighted average of the readings of all the sensors. In this computation, the weight for each sensor is the aforementioned value used to quantify its reliability. In an optional variant of the MSA algorithm that can be implemented easily, a running sum of the reliability value for each sensor at previous time steps as well as at the present time step is used as the weight of the sensor in calculating the weighted average at the present time step. In this variant, the weight of a sensor that continually fails gradually decreases, so that eventually, its influence over the output reading becomes minimal: In effect, the sensor system "learns" which sensors to trust and which not to trust. The MSA algorithm incorporates a criterion for deciding whether there remain enough sensor readings that

  14. ULTRACOOL FIELD BROWN DWARF CANDIDATES SELECTED AT 4.5 {mu}m

    SciTech Connect

    Eisenhardt, Peter R. M.; Griffith, Roger L.; Stern, Daniel; Mainzer, Amy; Wright, Edward L.; Ghez, A. M.; Konopacky, Quinn; Ashby, Matthew L. N.; Brodwin, Mark; Brown, Michael J. I.; Bussmann, R. S.; Dey, Arjun; Glikman, Eilat; Gonzalez, Anthony H.; Vollbach, David; Kirkpatrick, J. Davy; Wright, Shelley A.

    2010-06-15

    We have identified a sample of cool field brown dwarf candidates using IRAC data from the Spitzer Deep, Wide-Field Survey (SDWFS). The candidates were selected from 400,000 SDWFS sources with [4.5] {<=} 18.5 mag and were required to have [3.6] - [4.5] {>=} 1.5 and [4.5] - [8.0] {<=} 2.0 on the Vega system. The first color requirement selects objects redder than all but a handful of presently known brown dwarfs with spectral classes later than T7, while the second eliminates 14 probable reddened active galactic nuclei (AGNs). Optical detection of four of the remaining 18 sources implies they are likely also AGNs, leaving 14 brown dwarf candidates. For two of the brightest candidates (SDWFS J143524.44+335334.6 and SDWFS J143222.82+323746.5), the spectral energy distributions including near-infrared detections suggest a spectral class of {approx}T8. The proper motion is <0.''25 yr{sup -1}, consistent with expectations for a luminosity-inferred distance of >70 pc. The reddest brown dwarf candidate (SDWFS J143356.62+351849.2) has [3.6] - [4.5] = 2.24 and H - [4.5] > 5.7, redder than any published brown dwarf in these colors, and may be the first example of the elusive Y-dwarf spectral class. Models from Burrows et al. predict that larger numbers of cool brown dwarfs should be found for a Chabrier mass function. Suppressing the model [4.5] flux by a factor of 2, as indicated by previous work, brings the Burrows models and observations into reasonable agreement. The recently launched Wide-field Infrared Survey Explorer will probe a volume {approx}40x larger and should find hundreds of brown dwarfs cooler than T7.

  15. Phosphatidylinositol(4,5)bisphosphate and Phosphatidylinositol(4)phosphate in Plant Tissues 1

    PubMed Central

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

    1989-01-01

    Pea (Pisum sativum) leaf discs or swimming suspensions of Chlamydomonas eugametos were radiolabeled with [3H]myo-inositol or [32P]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. PMID:16666637

  16. Regulation of voltage-gated potassium channels by PI(4,5)P2

    PubMed Central

    Kruse, Martin; Hammond, Gerald R.V.

    2012-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) regulates activities of numerous ion channels including inwardly rectifying potassium (Kir) channels, KCNQ, TRP, and voltage-gated calcium channels. Several studies suggest that voltage-gated potassium (KV) channels might be regulated by PI(4,5)P2. Wide expression of KV channels in different cells suggests that such regulation could have broad physiological consequences. To study regulation of KV channels by PI(4,5)P2, we have coexpressed several of them in tsA-201 cells with a G protein–coupled receptor (M1R), a voltage-sensitive lipid 5-phosphatase (Dr-VSP), or an engineered fusion protein carrying both lipid 4-phosphatase and 5-phosphatase activity (pseudojanin). These tools deplete PI(4,5)P2 with application of muscarinic agonists, depolarization, or rapamycin, respectively. PI(4,5)P2 at the plasma membrane was monitored by Förster resonance energy transfer (FRET) from PH probes of PLCδ1 simultaneously with whole-cell recordings. Activation of Dr-VSP or recruitment of pseudojanin inhibited KV7.1, KV7.2/7.3, and Kir2.1 channel current by 90–95%. Activation of M1R inhibited KV7.2/7.3 current similarly. With these tools, we tested for potential PI(4,5)P2 regulation of activity of KV1.1/KVβ1.1, KV1.3, KV1.4, and KV1.5/KVβ1.3, KV2.1, KV3.4, KV4.2, KV4.3 (with different KChIPs and DPP6-s), and hERG/KCNE2. Interestingly, we found a substantial removal of inactivation for KV1.1/KVβ1.1 and KV3.4, resulting in up-regulation of current density upon activation of M1R but no changes in activity upon activating only VSP or pseudojanin. The other channels tested except possibly hERG showed no alteration in activity in any of the assays we used. In conclusion, a depletion of PI(4,5)P2 at the plasma membrane by enzymes does not seem to influence activity of most tested KV channels, whereas it does strongly inhibit members of the KV7 and Kir families. PMID:22851677

  17. 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.

  18. 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.

  19. Tert-butyl-2(4,5-dihydrogen-4,4,5,5-tetramethyl-3-O-1H-imidazole-3-cationic-1-oxyl-2-pyrrolidine-1-carboxylic ester displays novel cytotoxicity through reactive oxygen species-mediated oxidative damage in MCF-7 and MDA-MB-231 cells.

    PubMed

    Zhang, Yanjun; Guo, Juan; Zeng, Lihua; Zhang, Jie; Hui, Yanping; Liu, Junye; Qing, Xiangyang; Sun, Xiaoli; Guo, Guozhen

    2011-07-15

    The cytotoxicity of a new nitroxyl nitroxide radical, tert-butyl-2 (4,5-dihydrogen-4,4,5,5-tetramethyl-3-O-1H-imidazole-3-cationic-1-oxyl-2-pyrrolidine-1-carboxylic ester (L-NNP) was examined in MCF-7 and MDA-MB-231 cells. L-NNP treatment resulted in a significant growth inhibition in MCF-7 and MDA-MB-231 cells. Compared with control, 10, 30, and 50μg/ml L-NNP treatments for 48h induced significant cell and nuclei swelling, and organelle distension. The marked cell death was seen in a concentration- and time-dependant manner in L-NNP treated groups. The L-NNP treated group displayed a concentration-dependant increase in DNA double strand damage compared to the control and the 1Gy γ-rays exposure groups. These results suggest that L-NNP could result in more lethal genotoxicity than 1Gy γ-radiation. Based on mitochondrial alteration (membrane potential loss and SDH activity descend), DNA damage, an increase in MDA production, and GSH-PX inactivation, we predicate that L-NNP induces lipid oxidation and oxidative damage in MCF-7 and MDA-MB-231 cells. Since L-NNP initiated a significant increase in reactive oxygen species, which could largely be inhibited by NAC pretreatment, the overall data strongly suggest that the mechanism of cytotoxicity of L-NNP was its ability to act as a strong free radical, and significantly increase intracellular reactive oxygen species production. This led to intracellular oxidative damage, and antioxidant enzyme inactivation, resulting in cell death. We hypothesize that the greater cytotoxicity of L-NNP in MDA-MB-231 cells than in MCF-7 cells might be due to more ROS production in MDA-MB-231 cells, leading to more oxidative damage.

  20. 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.

  1. 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…

  2. 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

    2016-02-28

    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.

  3. 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

  4. A CURRICULUM GUIDE IN FOREIGN LANGUAGE--FRENCH IN GRADES 4, 5, AND 6.

    ERIC Educational Resources Information Center

    LUTZ, STEVEN; AND OTHERS

    THIS CURRICULUM GUIDE FOR A FRENCH FLES PROGRAM, FEATURING EDUCATIONAL TELEVISION IN COMBINATION WITH CLASSROOM INSTRUCTION BY LANGUAGE SPECIALISTS, REFLECTS FIVE YEARS' EXPERIENCE WITH THE PROGRAM IN PRINCE GEORGE'S COUNTY, MARYLAND. THE PROGRAM FOR GRADES 4, 5, AND 6 DESCRIBED IN THIS GUIDE HAS BEEN EVALUATED, IMPROVED, AND IMPLEMENTED AT THE…

  5. 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 (

  6. 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

  7. 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.

  8. Multiresistant Salmonella enterica serovar 4,[5],12:i:- in Europe: a new pandemic strain?

    PubMed

    Hopkins, K L; Kirchner, M; Guerra, B; Granier, S A; Lucarelli, C; Porrero, M C; Jakubczak, A; Threlfall, E J; Mevius, D J

    2010-06-03

    A marked increase in the prevalence of S. enterica serovar 4,[5],12:i:- with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines (R-type ASSuT) has been noted in food-borne infections and in pigs/pig meat in several European countries in the last ten years. One hundred and sixteen strains of S. enterica serovar 4,[5],12:i:- from humans, pigs and pig meat isolated in England and Wales, France, Germany, Italy, Poland, Spain and the Netherlands were further subtyped by phage typing, pulsed-field gel electrophoresis and multilocus variable number tandem repeat analysis to investigate the genetic relationship among strains. PCR was performed to identify the fljB flagellar gene and the genes encoding resistance to ampicillin, streptomycin, sulphonamides and tetracyclines. Class 1 and 2 integrase genes were also sought. Results indicate that genetically related serovar 4,[5],12:i:- strains of definitive phage types DT193 and DT120 with ampicillin, streptomycin, sulphonamide and tetracycline resistance encoded by blaTEM, strA-strB, sul2 and tet(B) have emerged in several European countries, with pigs the likely reservoir of infection. Control measures are urgently needed to reduce spread of infection to humans via the food chain and thereby prevent the possible pandemic spread of serovar 4,[5],12:i:- of R-type ASSuT as occurred with S. Typhimurium DT104 during the 1990s.

  9. 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.

  10. Characterization of Ffh of Mycobacterium tuberculosis and its interaction with 4.5S RNA.

    PubMed

    Palaniyandi, Kannan; Veerasamy, Malini; Narayanan, Sujatha

    2012-10-12

    Signal recognition particle (SRP) mediates targeting of proteins to appropriate cellular compartments, which is an important process in all living organisms. In prokaryotes, SRP consists of Ffh, a protein, and 4.5S RNA that recognizes signal peptide emerging from ribosomes. The SRP (Ffh) of one the most successful intracellular pathogen, Mycobacterium tuberculosis, has been investigated with respect to biochemical properties. In the present study, Ffh of M. tuberculosis was overexpressed and was confirmed to be a GTPase using thin layer chromatography and malachite green assay. The GTP binding ability was confirmed by GTP overlay assay. The 4.5S RNA sequence of M. tuberculosis was synthesized by in vitro transcription assay. The interaction between Ffh and 4.5S RNA was confirmed by overlay assay and RNA gel shift assay. The results show that the biochemical properties of M. tuberculosis Ffh have been conserved, and this is the first report that shows the interaction of components of SRP in M. tuberculosis, namely Ffh protein and 4.5S RNA.

  11. 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…

  12. Mathematics Pentathlon. A Manual of Directions and Official Tournament Rules. Division III. Grades 4-5.

    ERIC Educational Resources Information Center

    del Regato, John C.; And Others

    The Mathematics Pentathlon is a tournament of mathematics games held each spring since 1979 to promote the development of mathematical concepts and skills while fostering interaction among the educational community. There are five games in each of four divisions, for grades K-1, 2-3, 4-5, and 6-7. The focus is on active problem solving and…

  13. 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.

  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. 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…

  16. 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…

  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. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... materials directly to health-sciences professionals. An individual wishing a loan of library materials must... NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted materials... any interested person only in facilities provided by the Library for this purpose. The Director...

  5. Lymphocele formation after anterior lumbar interbody fusion at L4-5. Case report.

    PubMed

    Pee, Yong Hun; Kim, Ki Joon; Choi, Young-Geun; Jeon, Sang Hyeop; Park, Jong Dae; Lee, Sang-Ho

    2007-11-01

    In this report, the authors present the case of patient with a lymphocele in the retroperitoneal area following anterior lumbar interbody fusion at L4-5. A lymphocele is a rare complication of spinal operations, especially lower lumbar spinal surgeries. The authors discuss this complicating factor and describe its features and treatments.

  6. 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...

  7. 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…

  8. 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

  9. 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

  10. Job-Sharing at the Greater Victoria Public Library.

    ERIC Educational Resources Information Center

    Miller, Don

    1978-01-01

    Describes the problems associated with the management of part-time library employees and some solutions afforded by a job sharing arrangement in use at the Greater Victoria Public Library. This is a voluntary work arrangement, changing formerly full-time positions into multiple part-time positions. (JVP)

  11. The search for new antiarrhythmics in the group of chirally 1,2-aminoalcohols. I. 3',4',5'-trimethoxybenzoic acid esters of optically active N,N'-dimethyl-N,N'-bis-(1-hydroxybutyl-2) ethylenediamines.

    PubMed

    Eckstein, M; Herdegen, E

    1980-01-01

    Both enantiomeric (2S, 2'S) and (2'R) N, N'-dimethyl-N, N-bis (1-hydroxybutyl-2)-ethylenediamines (Table 1) were obtained by methylation of the corresponding N,N'-ethylene-bis-2-aminobutanols-1. The esterification of the former aminoalcohols with 3, 4, 5-trimethoxybenzoic acid gave the both enantiomeric in title named esters (Table 2). The isomer with S configuration at both chirally center (C2 and C2), has a particularly strong antiarrhythmic properties (about 10-20 greater than quinidine or procaine amide in different experimental arrhythmia models in animals. The 2R,2'R enantiomere is 10-100 times less active one. It seems that the antiarrhythmic activity of this new group of antiarrhythmically active compounds, derivatives of chirally 1, 2-aminoalcohols is connected with spatial configuration.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Photometry of Scattered Disk Objects at 3.6 and 4.5 μm

    NASA Astrophysics Data System (ADS)

    Melton, Chad A.; Emery, Joshua P.; Pinilla-Alonso, Noemi; Mommert, Michael; Lejoly, Cassandra; Trilling, David E.

    2016-10-01

    Scattered disk objects (SDO) are some of the most intriguing of the estimated 100,000 icy bodies located in the outer Solar System. SDOs have been gravitationally disturbed and scattered by the orbital migration of Neptune. The surface compositions of these objects provide a window into formation conditions and dynamics of the outer Solar System. Characterization of volatiles and organic materials, in particular, provide important constraints on formation conditions and subsequent surface processing of these objects. We measured fluxes of 38 SDOs at 3.6 and 4.5 μm using the Infrared Array Camera (IRAC) aboard the NASA Spitzer Space Telescope in order to characterize volatiles, silicates, and complex organics on their surfaces. Albedos calculated from these fluxes are combined with broadband albedos from ground-based observations at shorter wavelengths (spanning 0.55 – 2.22 μm) to provide spectrophotometry from 0.5 to 4.5 μm. Much of those ground-based data are from previously published literature. However, we have also conducted new ground-based Y, J, H, K observations of several of the targets. Sizes and visible geometric albedos, which are required to convert IRAC fluxes to geometric albedos, were extracted from published literature when available and computed from absolute magnitudes otherwise. Data were available to construct complete 0.55 to 4.5 μm spectrophotometric curves for 14 SDOs and partial curves for the remaining 24 SDOs. The resulting spectrophotometry of these 38 SDOs indicates a wide range of surface compositions. Several of the SDOs we observed show red visible and near-infrared spectral slopes and strong absorptions at 3.6 and 4.5 μm. These absorption features suggest the presence of complex organics. Other SDOs appear red as well, but show only moderate absorptions at 3.6 and 4.5 μm. Moderate absorption features at these wavelengths may indicate a mixture of H2O ice and refractory material on the surface. Finally, some objects show no

  17. Prevention of Canine Leishmaniosis in a Hyper-Endemic Area Using a Combination of 10% Imidacloprid/4.5% Flumethrin

    PubMed Central

    Otranto, Domenico; Dantas-Torres, Filipe; de Caprariis, Donato; Di Paola, Giancarlo; Tarallo, Viviana D.; Latrofa, Maria S.; Lia, Riccardo P.; Annoscia, Giada; Breitshwerdt, Edward B.; Cantacessi, Cinzia; Capelli, Gioia; Stanneck, Dorothee

    2013-01-01

    Background Dogs are the main reservoir hosts of Leishmania infantum, the agent of human zoonotic visceral leishmaniosis. This study investigated the efficacy of a polymer matrix collar containing a combination of 10% imidacloprid and 4.5% flumethrin as a novel prophylactic measure to prevent L. infantum infections in young dogs from a hyper-endemic area of southern Italy, with a view towards enhancing current control strategies against both human and canine leishmaniosis. Methodology/Principal Findings The study was carried out on 124 young dogs, of which 63 were collared (Group A) while 61 were left untreated (Group B), from March-April 2011 until March 2012. Blood and skin samples were collected at baseline (April 2011) and at the first, second, third and fourth follow-up time points (July, September 2011 and November 2011, and March 2012, respectively). Bone marrow and conjunctiva were sampled at baseline and at the fourth follow-up. Serological, cytological and molecular tests were performed to detect the presence of L. infantum in the different tissues collected. At the end of the trial, no dog from Group A proved positive for L. infantum at any follow-up, whereas 22 dogs from Group B were infected (incidence density rate = 45.1%); therefore, the combination of 10% imidacloprid and 4.5% flumethrin was 100% efficacious for the prevention of L. infantum infection in young dogs prior to their first exposure to the parasite in a hyper-endemic area for CanL. Conclusions The use of collars containing 10% imidacloprid and 4.5% flumethrin conferred long-term protection against infection by L. infantum to dogs located in a hyper-endemic area, thus representing a reliable and sustainable strategy to decrease the frequency and spread of this disease among the canine population which will ultimately result in the reduction of associated risks to human health. PMID:23451043

  18. 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.

  19. Regulation of voltage-gated potassium channels by PI(4,5)P2.

    PubMed

    Kruse, Martin; Hammond, Gerald R V; Hille, Bertil

    2012-08-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) regulates activities of numerous ion channels including inwardly rectifying potassium (K(ir)) channels, KCNQ, TRP, and voltage-gated calcium channels. Several studies suggest that voltage-gated potassium (K(V)) channels might be regulated by PI(4,5)P(2). Wide expression of K(V) channels in different cells suggests that such regulation could have broad physiological consequences. To study regulation of K(V) channels by PI(4,5)P(2), we have coexpressed several of them in tsA-201 cells with a G protein-coupled receptor (M(1)R), a voltage-sensitive lipid 5-phosphatase (Dr-VSP), or an engineered fusion protein carrying both lipid 4-phosphatase and 5-phosphatase activity (pseudojanin). These tools deplete PI(4,5)P(2) with application of muscarinic agonists, depolarization, or rapamycin, respectively. PI(4,5)P(2) at the plasma membrane was monitored by Förster resonance energy transfer (FRET) from PH probes of PLCδ1 simultaneously with whole-cell recordings. Activation of Dr-VSP or recruitment of pseudojanin inhibited K(V)7.1, K(V)7.2/7.3, and K(ir)2.1 channel current by 90-95%. Activation of M(1)R inhibited K(V)7.2/7.3 current similarly. With these tools, we tested for potential PI(4,5)P(2) regulation of activity of K(V)1.1/K(V)β1.1, K(V)1.3, K(V)1.4, and K(V)1.5/K(V)β1.3, K(V)2.1, K(V)3.4, K(V)4.2, K(V)4.3 (with different KChIPs and DPP6-s), and hERG/KCNE2. Interestingly, we found a substantial removal of inactivation for K(V)1.1/K(V)β1.1 and K(V)3.4, resulting in up-regulation of current density upon activation of M(1)R but no changes in activity upon activating only VSP or pseudojanin. The other channels tested except possibly hERG showed no alteration in activity in any of the assays we used. In conclusion, a depletion of PI(4,5)P(2) at the plasma membrane by enzymes does not seem to influence activity of most tested K(V) channels, whereas it does strongly inhibit members of the K(V)7 and K(ir) families. PMID

  20. Fragrance material review on 3,4,5,6,6-pentamethylheptan-2-ol.

    PubMed

    McGinty, D; Scognamiglio, J; Letizia, C S; Api, A M

    2010-07-01

    A toxicologic and dermatologic review of 3,4,5,6,6-pentamethylheptan-2-ol when used as a fragrance ingredient is presented. 3,4,5,6,6-Pentamethylheptan-2-ol is a member of the fragrance structural group branched chain saturated alcohols. The common characteristic structural elements of the alcohols with saturated branched chain are one hydroxyl group per molecule, and a C(4)-C(12) carbon chain with one or several methyl side chains. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire branched chain saturated alcohol group will be published simultaneously with this document; please refer to Belsito et al. (2010) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances.

  1. Molecular typing of monophasic Salmonella 4,[5]:i:- strains isolated in Belgium (2008-2011).

    PubMed

    Boland, Cécile; Bertrand, Sophie; Mattheus, Wesley; Dierick, Katelijne; Wattiau, Pierre

    2014-01-31

    To assess the distribution of Salmonella 4,[5]:i:- subtypes in the Belgian food chain and compare it to the subtypes associated with human infections, a molecular assessment was initiated. Two hundred fifty-three Salmonella isolates serotyped as 4,[5]:i:- during the period 2008-2011 in Belgium and originating from animal productions, food or human clinical samples were analysed by a specific duplex PCR. One hundred ninety-four isolates (76.7%) fit the profile of a S. Typhimurium monophasic variant as defined by the European Food Safety Authority. The other isolates possessed but did not express the phase II flagellin gene (23.3%). Multiple Locus Variable Number of Tandem Repeats Analysis (MLVA) revealed many but closely related profiles in the fljB-negative S. Typhimurium monophasic variant isolates. Some MLVA types were associated with both human and animal isolates but no unique source of human contamination could be demonstrated.

  2. Electronic considerations in the mutagenesis of some 4,5-bridged chrysenes

    SciTech Connect

    Lee-Ruff, E.; Raj, A.S.; Kruk, H.; Katz, M.

    1987-01-01

    The mutagenic activity of four 4,5-bridged chrysene derivatives, benz(a)aceanthrylene, and 5-methylchrysene was examined using histidine auxotrophic strains TA98 and TA100 of Salmonella typhimurium. All compounds showed a positive mutagenic response with both TA100 and TA98 in the presence of S-9. A correlation between the electronic character of the bridging group and mutagenic activity for the chrysene derivatives is proposed.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

    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 4.5K 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 80to14.5K and a helium stage establishing 5mW at 4.5K. Both stages use microporous activated carbon as the adsorption material. The two cooler stages need about 3.5W of total input power and are heat sunk at two passive radiators at temperatures of about 50 and 80K—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 4.5mW at 4.5K with a long-term temperature stability of 1mK and an input power of 1.96W. So far, the cooler has operated continuously for a period of 2.5months and has not shown any sign of performance degradation.

  5. 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.

  6. 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.

  7. Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate.

    PubMed Central

    Meyer, T; Stryer, L

    1990-01-01

    Many hormonal, neurotransmitter, and sensory stimuli trigger the formation of inositol 1,4,5-trisphosphate, which in turn releases calcium from intracellular stores. We report here that inositol 1,4,5-trisphosphate-induced calcium release from saponin-permeabilized rat basophilic leukemia cells at 37 degrees C is markedly biphasic, in contrast with nearly monophasic release kinetics at 11 degrees C. Hepatoma, PC-12 neuronal cells, and several other cell types exhibit similar biphasic release at 37 degrees C. The biphasic kinetics are not due to degradation of inositol 1,4,5-trisphosphate or to increased Ca2(+)-ATPase pump activity. Biphasic calcium release was also seen when ATP was quenched to less than 0.4 microM by adding hexokinase and glucose, suggesting that phosphorylation is not involved. External calcium (100 nM-600 nM) range had little influence on the biphasic kinetics. Rapid-mixing experiments revealed that rapid efflux of calcium is followed in approximately 0.5 s by a 30-fold slower efflux. Most striking, successive additions of the same amount of inositol 1,4,5-trisphosphate induced short bursts of calcium release of similar size. This retention of responsiveness, which we term increment detection, may be a distinct mode of signal transduction. Like inactivation and adaptation, increment detection gives rise to transient responses to sustained stimuli. Systems exhibiting inactivation, adaptation, and increment detection differ in their responsiveness (none, partial, and full, respectively) to stepwise increases in stimulus intensity. Increment detection could be advantageous in generating receptor-triggered calcium oscillations. Images PMID:2339124

  8. 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.

  9. 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

  10. 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.

  11. Poloidal monochromatic pulsations in Pc4-5 range observed in the Earth magnetosphere

    NASA Astrophysics Data System (ADS)

    Belakhovsky, Vladimir

    Poloidal monochromatic pulsations in Pc4-5 range observed in the Earth magnetosphere Belakhovsky V.B.1, Pilipenko V.A.2 1 - Polar Geophysical Institute, Apatity, Russia 2 - Institute of Physics of the Earth, Moscow, Russia Monochromatic geomagnetic pulsations in the Pc4-5 frequency range in the morning sector for some events in 2007-2008 years were studied using GOES, THEMIS, and ETS spacecrafts. The satellite observations showed that these pulsations are a poloidal-type fundamental mode of Alfven field line oscillations with the dominant radial and field-aligned magnetic components. The observed pulsations are small-scale in azimuthal direction; it excited during the low geomagnetic activity and are quite similar to Pg type pulsations. Contrary to typical Pg, these pulsations practically cannot be seen on the CARISMA magnetometers. The observed magnetic pulsations were accompanied by the simultaneous pulsations in the fluxes of energetic electrons and protons, as seen by LANL satellites with a great modulation depth. A strong increase of the electron density in the magnetosphere was found before the onset of the geomagnetic pulsations. As seen by THEMIS satellites these pulsations propagate in sunward direction, i.e. in the direction of electron drift in the morning sector. We suppose that the injection of energetic electrons may be responsible for the excitation of the poloidal Pc4-5 pulsations at the morning flank of the magnetosphere, though specific excitation mechanism is still unknown.

  12. 9-Phenyl-4,5-diaza-9H-fluoren-9-ol monohydrate

    PubMed Central

    Yin, Guo-Jie; Yang, Gang-Bin; Wang, Shi-Min

    2012-01-01

    The title compound, C17H12N2O·H2O, was synthesized by the reaction of 4,5-diaza­fluoren-9-one with a Grignard reagent in ether (the reaction mixture being hydrolysed with saturated NH4Cl solution), and crystallizes with two organic mol­ecules and two water mol­ecules in the asymmetric unit. The 4,5-diaza­fluorene fragment is approximately planar, with r.m.s. deviations of 0.0448 and 0.0198 Å in the two mol­ecules. The dihedral angles between the 4,5-diaza­fluorene planes and the phenyl ring are 80.49 (6) and 76.57 (7)°. The crystal packing features O—H⋯N and O—H⋯O hydrogen bonds involving the bridging solvent water mol­ecules, which link the mol­ecules into a three-dimensional network. PMID:22719589

  13. 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.

  14. Metabolism of inositol(1,4,5)trisphosphate by a soluble enzyme fraction from pea (Pisum sativum) roots

    SciTech Connect

    Drobak, B.K.; Watkins, P.A.C.; Roberts, K. ); Chattaway, J.A. Univ. of East Anglia, Norwich ); Dawson, A.P. )

    1991-02-01

    Metabolism of the putative messenger molecule D-myo-inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) in plant cells has been studied using a soluble fraction from pea (pisum sativum) roots as enzyme source and (5-{sup 32}P)Ins(1,4,5)P{sub 3} and (2-{sup 3}H)Ins(1,4,5)P{sub 3} as tracers. Ins(1,4,5)P{sub 3} was rapidly converted into both lower and higher inositol phosphates. The major dephosphorylation product was inositol (4,5) bisphosphate (Ins(4,5)P{sub 2}) whereas inositol(1,4)bisphosphate (Ins(1,4)P{sub 2}) was only present in very small quantities throughout a 15 minute incubation period. In addition to these compounds, small amounts of nine other metabolites were produced including inositol and inositol(1,4,5,X)P{sub 4}. Dephosphorylation of Ins(1,4,5)P{sub 3} to Ins(4,5)P{sub 2} was dependent on Ins(1,4,5)P{sub 3} concentration and was partially inhibited by the phosphohydrolase inhibitors 2,3-diphosphoglycerate, glucose 6-phosphate, and p-nitrophenylphosphate. Conversion of Ins(1,4,5)P{sub 3} to Ins(4,5)P{sub 2} and Ins(1,4,5,X)P{sub 4} was inhibited by 55 micromolar Ca{sup 2+}. This study demonstrates that enzymes are present in plant tissues which are capable of rapidly converting Ins(1,4,5)P{sub 3} and that pathways of inositol phosphate metabolism exist which may prove to be unique to the plant kingdom.

  15. Inositol 1,4,5-trisphosphate-induced calcium release in the organelle layers of the stratified, intact egg of Xenopus laevis

    PubMed Central

    1990-01-01

    Using double-barreled, Ca2(+)-sensitive microelectrodes, we have examined the characteristics of the Ca2+ release by inositol 1,4,5- trisphosphate (Ins(1,4,5)P3) in the various layers of Xenopus laevis eggs in which the organelles had been stratified by centrifugation. Centrifugation of living eggs stratifies the organelles yet retains them in the normal cytoplasmic milieu. The local increase in intracellular free Ca2+ in each layer was directly measured under physiological conditions using theta-tubing, double-barreled, Ca2(+)- sensitive microelectrodes in which one barrel was filled with the Ca2+ sensor and the other was filled with Ins(1,4,5)P3 for microinjection. The two tips of these electrodes were very close to each other (3 microns apart) enabling us to measure the kinetics of both the highly localized intracellular Ca2+ release and its subsequent removal in response to Ins(1,4,5)P3 injection. Upon Ins(1,4,5)P3 injection, the ER- enriched layer exhibited the largest release of Ca2+ in a dosage- dependent manner, whereas the other layers, mitochondria, lipid, and yolk, released 10-fold less Ca2+ in a dosage-independent manner. The removal of released Ca2+ took place within approximately 1 min. The sensitivity to Ins(1,4,5)P3 and the time course of intracellular Ca2+ release in the unstratified (unactivated) egg is nearly identical to that observed in the ER layer of the stratified egg. Our data suggest that the ER is the major organelle of the Ins(1,4,5)P3-sensitive Ca2+ store in the egg of Xenopus laevis. PMID:2324195

  16. Sepsis After Cardiac Surgery Early in Infancy and Adverse 4.5-Year Neurocognitive Outcomes

    PubMed Central

    Sidhu, Naveen; Joffe, Ari R; Doughty, Paul; Vatanpour, Shabnam; Dinu, Irina; Alton, Gwen; Acton, Bryan; Robertson, Charlene M T

    2015-01-01

    Background We aimed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy. Methods and Results A secondary analysis from a prospective inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009. Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale, performance, and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence. Perioperative variables were collected prospectively, and confirmation of blood culture–positive sepsis was done retrospectively. Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined. Sepsis occurred in 97 of 502 patients (19%) overall and in 76 of 396 survivors (19%) with 4.5-year follow-up. By 4.5 years, there were 91 (18%) deaths, and 396 of 411 survivors (96%) had follow-up completed. Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of −13.6 (95% CI −21.3 to −5.9; P =0.001). Sepsis perioperatively was associated with performance and verbal intelligence quotients, with a trend for full-scale intelligence quotient (P =0.058) on multivariable regression. The regression coefficient for sepsis was strongest for performance intelligence quotient (−5.31; 95% CI −9.84 to −0.78; P =0.022). Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years. Conclusions Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression. Quality improvement to

  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. 4,4',5,5'-Tetracarboxy-2,2'-bipyridine Ru(II) sensitizers for dye-sensitized solar cells.

    PubMed

    Chou, Chun-Cheng; Hu, Fa-Chun; Wu, Kuan-Lin; Duan, Tainan; Chi, Yun; Liu, Shih-Hung; Lee, Gene-Hsiang; Chou, Pi-Tai

    2014-08-18

    Two Ru(II) sensitizers TCR-1 and TCR-2 bearing four carboxy anchoring groups were prepared using 4,4',5,5'-tetraethoxycarbonyl-2,2'-bipyridine chelate and 4-(5-hexylthien-2-yl)-2-(3-trifluoromethyl-1H-pyrazol-5-yl)pyridine and 6-t-butyl-1-(3-trifluoromethyl-1H-pyrazol-5-yl)isoquinoline, respectively. Dissolution of these sensitizers in DMF solution afforded a light green solution up to 10(-5) M, for which their color gradually turned red upon further dilution and deposition on the surface of a TiO2 photoanode due to the spontaneous deprotonation of carboxylic acid groups. These sensitizers were characterized using electrochemical means and structural analysis time-dependent density functional theory (TDDFT) simulation and were also subjected to actual device fabrication. The as-fabricated DSC devices showed overall efficiencies η = 6.16% and 6.23% versus their 4,4'-dicarboxy counterparts TFRS-2 and TFRS-52 with higher efficiencies of 7.57% and 8.09%, using electrolyte with 0.2 M LiI additive. Their inferior efficiencies are possibly caused by the combination of blue-shifted absorption on TiO2, inadequate dye loading, and the perpendicularly oriented central carboxy groups.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Men Face Greater Risk of Cardiac Arrest

    MedlinePlus

    ... page: https://medlineplus.gov/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 ...

  4. 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

  5. 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

  6. Asymmetric Synthesis of 2,4,5-Trisubstituted Δ2-Thiazolines

    PubMed Central

    Bengtsson, Christoffer; Nelander, Hanna; Almqvist, Fredrik

    2013-01-01

    Δ2-Thiazolines are interesting heterocycles that display a wide variety of biological characteristics. They are also common in chiral ligands used for asymmetric syntheses and as synthetic intermediates. Herein, we present asymmetric routes to 2,4,5-trisubstituted Δ2-thiazolines. These Δ2-thiazolines were synthesized from readily accessible/commercially available α,β-unsaturated methyl esters through a Sharpless asymmetric dihydroxylation and an O→N acyl migration reaction as key steps. The final products were obtained in good yields with up to 97% enantiomeric excess. PMID:23776083

  7. 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.

  8. SeizAlert could give patients 4.5 hour warning of seizure

    ScienceCinema

    Dr. Lee Hively and Kara Kruse

    2016-07-12

    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.

  9. Evalution Of A 4.5-kW D-100 Thruster With Anode Layer

    NASA Technical Reports Server (NTRS)

    Garner, C. E.; Tverdokhlebov, S. O.; Semenkin, A. V.; Garkusha, V. I.

    1996-01-01

    Design characteristics and performance data of a 4.5-kW, thruster with anode layer (TAL) developed at the Central Research Institue for Machine Building (TsNIIMASH) are presented. The TAL is designated the D-100 with a discharge chamber of outer diameter approximately 100mm. Performance characteristics demonstrated by the D-100 and life estimates by TsNIIMASH make this thruster an excellent candidate for a wide range of station keeping, orbit raising, orbit maneuvering and JPL planetary missions.

  10. Design, fabrication and characterization of an AWG at 4.5 µm.

    PubMed

    Barritault, Pierre; Brun, Mickael; Labeye, Pierre; Hartmann, Jean-Michel; Boulila, Fahem; Carras, Mathieu; Nicoletti, Sergio

    2015-10-01

    In this paper, we present the design, the fabrication and the characterization of an Arrayed Waveguide Grating (AWG) based on a SiGe graded index waveguide platform, operating at 4.5 µm. These devices were specifically designed to work together with an array of Distributed Feedback Bragg Quantum Cascade Lasers (DFB-QCL) emitting at different wavelengths. The AWG enables to combine the different light sources into a single output and the design adopted allows to maximize transmission over the entire spectral range defined by the array of DFB-QCLs.

  11. 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

  12. 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

  13. 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

  14. 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

  15. A compact post-acceleration beam chopper for a 4.5 MV Dynamitron pulsed neutron generator

    NASA Astrophysics Data System (ADS)

    Matsuyama, S.; Fujisawa, M.; Baba, M.; Iwasaki, T.; Iwasaki, S.; Sakamoto, R.; Hirakawa, N.; Sugiyama, K.

    1994-08-01

    A post-acceleration beam chopper (PACS) has been installed for a 4.5 MV Dynamitron accelerator to improve the energy resolution of neutron time-of-flight (TOF) experiments by shortening the duration of the ion beam pulses. The PACS sweeps the accelerated ion pulses across a chopping slit and eliminates the tails of the beam pulses. It operates sinusoidally at a frequency of 8 MHz with a maximum voltage of 10 kV peak to peak in synchronization with the accelerated ion pulses. The high voltage generator of the PACS was constructed of commercially available amplifiers and components, which realized easy maintenance and low cost. The PACS proved to be very effective to improve the pulse shape and has been applied for double-differential neutron emission cross section measurements.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction.

    PubMed

    Lewis, Aurélia E; Sommer, Lilly; Arntzen, Magnus Ø; Strahm, Yvan; Morrice, Nicholas A; Divecha, Nullin; D'Santos, Clive S

    2011-02-01

    Considerable insight into phosphoinositide-regulated cytoplasmic functions has been gained by identifying phosphoinositide-effector proteins. Phosphoinositide-regulated nuclear functions however are fewer and less clear. To address this, we established a proteomic method based on neomycin extraction of intact nuclei to enrich for nuclear phosphoinositide-effector proteins. We identified 168 proteins harboring phosphoinositide-binding domains. Although the vast majority of these contained lysine/arginine-rich patches with the following motif, K/R-(X(n= 3-7)-K-X-K/R-K/R, we also identified a smaller subset of known phosphoinositide-binding proteins containing pleckstrin homology or plant homeodomain modules. Proteins with no prior history of phosphoinositide interaction were identified, some of which have functional roles in RNA splicing and processing and chromatin assembly. The remaining proteins represent potentially other novel nuclear phosphoinositide-effector proteins and as such strengthen our appreciation of phosphoinositide-regulated nuclear functions. DNA topology was exemplar among these: Biochemical assays validated our proteomic data supporting a direct interaction between phosphatidylinositol 4,5-bisphosphate and DNA Topoisomerase IIα. In addition, a subset of neomycin extracted proteins were further validated as phosphatidyl 4,5-bisphosphate-interacting proteins by quantitative lipid pull downs. In summary, data sets such as this serve as a resource for a global view of phosphoinositide-regulated nuclear functions.

  1. Diffusing capacity and spirometry following a 60-minute dive to 4.5 meters.

    PubMed

    Koehle, M S; Hodges, A N H; Lynn, B M; Rachich, M F; McKenzie, D C

    2006-01-01

    The purpose of this study was to assess the contribution of SCUBA to the pulmonary effects of diving to 4.5 meters depth in healthy subjects using a randomized crossover control condition. Ten healthy divers performed two 60-minute 'dives' using SCUBA in a swimming pool. The non-immersed 1 ATA SCUBA control exposure took place at ambient pressure in the laboratory. Thirty minutes prior to, and 30 and 90 minutes post-exposure, FVC (forced vital capacity), FEV1.0 (forced expired volume), peak expiratory flow rate (PEFR), diffusing capacity (DL(co)), heart rate (HR) and temperature were measured. No significant differences were noted in HR, temperature or spirometry between the two conditions. A significant reduction in diffusing capacity occurred at 30 and 90 minutes after the pool dive (9.3% and 15.1%, respectively, p < 0.05). There was no concordant change in DL(co) following the non-immersed 1 ATA SCUBA control. Thus, a pool dive to 4.5 meters for 60 minutes causes a decrease in DL(co), without a change in spirometry, while breathing from SCUBA equipment without immersion causes no significant change in lung function.

  2. The Inositol 1,4,5-triphosphate kinase1 gene affects olfactory reception in Drosophila melanogaster.

    PubMed

    Gomez-Diaz, Carolina; Martin, Fernando; Alcorta, Esther

    2006-03-01

    The Inositol 1,4,5-triphosphate (IP3) route is one of the two main transduction cascades that mediate olfactory reception in Drosophila melanogaster. The activity of IP3 kinase1 reduces the levels of this substrate by phosphorylation into inositol 1,3,4,5-tetrakiphosphate (IP4). We show here that the gene is expressed in olfactory sensory organs as well as in the rest of the head. To evaluate in vivo the olfactory functional effects of up-regulating IP3K1, individuals with directed genetic changes at the reception level only were generated using the UAS/Gal4 method. In this report, we described the consequences in olfactory perception of overexpressing the IP3Kinase1 gene at eight different olfactory receptor-neuron subsets. Six out of the eight studied Gal-4/UAS-IP3K1 hybrids displayed abnormal behavioral responses to ethyl acetate, acetone, ethanol or propionaldehyde. Specific behavioral defects corresponded to the particular neuronal olfactory profile. These data confirm the role of the IP3kinase1 gene, and consequently the IP3 transduction cascade, in mediating olfactory information at the reception level.

  3. Phosphatidylinositol 4,5-bisphosphate formation in rabbit skeletal and heart muscle membranes.

    PubMed

    Varsányi, M; Messer, M; Brandt, N R; Heilmeyer, L M

    1986-08-14

    Incubation of rabbit skeletal muscle microsomes or isolated triads with gamma 32P-ATP/Mg2+ in the absence and in the presence of added phosphatidylinositol resulted in the formation of phosphatidylinositol 4-phosphate catalyzed by phosphatidylinositol kinase. When phosphatidylinositol 4-phosphate was added as exogenous substrate, phosphatidylinositol 4,5-bisphosphate was also formed demonstrating the presence of a membrane bound phosphatidylinositol 4-phosphate kinase. Triads were broken mechanically in a French press and separated on a continuous sucrose gradient. Incubation of these fractions with gamma 32P-ATP/Mg2+ resulted in a rapid labeling of phospholipid in a membrane fraction banding between transverse tubules and the terminal cisternae. Partial triad breakage and triad reformation experiments indicated that this phosphatidylinositol kinase was associated with T-tubules. When exogenous phosphatidylinositol 4-phosphate was employed as substrate phosphatidylinositol 4,5-bisphosphate and phosphatidic acid were formed, indicating the presence of all the enzymes of the polyphosphoinositide signaling system in this special membrane fraction. In contrast, heart muscle microsomes or plasma membranes can catalyze this reaction sequence from endogenous formed phosphatidylinositol 4-phosphate.

  4. Hailstones across the Greater Sydney Metropolitan Area

    NASA Astrophysics Data System (ADS)

    Rasuly, A. A.; Cheung, K. K. W.; McBurney, B.

    2014-11-01

    This study addresses the recent climatology of hail occurrence in the Greater Metropolitan Severe Thunderstorm Warning Area (GMSTWA) of New South Wales, Australia, which is a sprawling suburban area, with a population of nearly 4.7 million and one of Australia's largest metropolis. The main objective is to highlight the recent temporal-spatial fluctuations of hailstone frequencies and magnitudes for each of recognized and vastly inhabited Local Government Areas (LGAs). The relevant hail event data from 1989 to 2013 were initially derived from the severe storm archive of Australian Bureau of Meteorology. A climatologically oriented GIS technique was applied in the examining and mapping procedure of all hail events and hail days reported throughout the study area. By applying a specific criterion, all severe hails (defined as 2 cm or more in diameter) were cautiously selected and then imported into the ArcGIS software for relevant analysis. Appropriate data layers were stored in a unique database to allow logical integration of the data directly into some geoprocessing functions, mainly for querying, analyzing and mapping purposes in a model-builder setting. The database includes 357 hailstones with sizes 2-11 cm and occurred in 169 hail days across the region during the past 25 years. The models have established that hailstones are neither temporally nor spatially uniform in magnitude throughout the study area. Temporal analysis indicated that most of hail events occurred predominately in the afternoons with peak time of 1-5 p.m. EST. They were particularly common in spring and summer, and reached maximum frequency in November and December. There was an average of 14.3 events each year, but a significant decreasing trend in terms of hail frequency and associated magnitude in the recent years has been identified. In turn, spatial models also established three main distribution patterns over the study area, which include the Sydney Metropolitan, coastal and pronounced

  5. 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.

  6. Multi-satellite study of the excitation of Pc3 and Pc4-5 ULF waves and their penetration across the plasmapause during the 2003 Halloween superstorm

    NASA Astrophysics Data System (ADS)

    Balasis, G.; Daglis, I. A.; Mann, I. R.; Papadimitriou, C.; Zesta, E.; Georgiou, M.; Haagmans, R.; Tsinganos, K.

    2015-10-01

    We use multi-satellite and ground-based magnetic data to investigate the concurrent characteristics of Pc3 (22-100 mHz) and Pc4-5 (1-22 mHz) ultra-low-frequency (ULF) waves on the 31 October 2003 during the Halloween magnetic superstorm. ULF waves are seen in the Earth's magnetosphere, topside ionosphere, and Earth's surface, enabling an examination of their propagation characteristics. We employ a time-frequency analysis technique and examine data from when the Cluster and CHAMP spacecraft were in good local time (LT) conjunction near the dayside noon-midnight meridian. We find clear evidence of the excitation of both Pc3 and Pc4-5 waves, but more significantly we find a clear separation in the L shell of occurrence of the Pc4-5 and Pc3 waves in the equatorial inner magnetosphere, separated by the density gradients at the plasmapause boundary layer. A key finding of the wavelet spectral analysis of data collected from the Geotail, Cluster, and CHAMP spacecraft and the CARISMA and GIMA magnetometer networks was a remarkably clear transition of the waves' frequency into dominance in a higher-frequency regime within the Pc3 range. Analysis of the local field line resonance frequency suggests that the separation of the Pc4-5 and Pc3 emissions across the plasmapause is consistent with the structure of the inhomogeneous field line resonance Alfvén continuum. The Pc4-5 waves are consistent with direct excitation by the solar wind in the plasma trough, as well as Pc3 wave absorption in the plasmasphere following excitation by upstream waves originating at the bow shock in the local noon sector. However, despite good solar wind coverage, our study was not able to unambiguously identify a clear explanation for the sharp universal time (UT) onset of the discrete frequency and large-amplitude Pc3 wave power.

  7. Synergistic effects of inositol 1,3,4,5-tetrakisphosphate on inositol 2,4,5-triphosphate-stimulated Ca2+ release do not involve direct interaction of inositol 1,3,4,5-tetrakisphosphate with inositol triphosphate-binding sites.

    PubMed Central

    Loomis-Husselbee, J W; Cullen, P J; Dreikausen, U E; Irvine, R F; Dawson, A P

    1996-01-01

    We have previously found that for permeabilized L1210 cells, low micromolar concentrations of Ins(1,3,4,5)P4 added prior to Ins(2,4,5)P3 enhance the effects of suboptimal concentrations of Ins(2,4,5)P3 in causing Ca2+ release from InsP3-sensitive Ca2+ stores [Cullen, Irvine and Dawson (1990) Biochem J. 271, 549-553]. If this was due either to some conversion of added Ins(1,3,4,5)P4 into Ins(1,4,5)P3 by the 3-phosphatase, or to Ins(1,3,4,5)P4 acting as a weak (or partial) agonist on the InsP3 receptor it would be expected that,in the presence of thimerosal to sensitize the InsP3 receptor, the dose-response curve to Ins(1,3,4,5)P4 would be left-shifted by the same extent as that of Ins(1,4,5)P3. This was found not to be the case; the dose-response curve to Ins(1,3,4,5)P4 was not shifted at all by thimerosal. Furthermore, L-Ins(1,3,4,5)P4, which can displace radiolabelled D-Ins(1,3,4,5)P4 but not D-Ins(1,4,5)P3 from their respective high-affinity binding sites, mimicked the effects of D-Ins(1,3,4,5)P4 in enhancing the slow phase of Ins(2,4,5)P3-stimulated Ca2+ release. Ins(1,3,4,5)P4 caused an increase in magnitude of the slow phase of InsP3-stimulated Ca2+ release leaving the magnitude of the fast phase unaltered, in contrast to increasing Ins(2,4,5)P3 concentrations which increased the size of both phases. In addition, Ins(1,3,4,5)P4 decreased the rate constant for the slow phase of Ca2+ release. These findings point strongly to the conclusion that InsP4 is not working directly via the InsP3 receptor but indirectly via an InsP4 receptor. PMID:8615774

  8. 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

  9. 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.

  10. Disodium 4,5,6-trihy­droxy­benzene-1,3-disulfonate dihydrate

    PubMed Central

    Song, E.; Podschun, J.; Wilberts, H.; Beginn, U.; Reuter, H.

    2010-01-01

    In the title compound, 2Na+·C6H4O9S2 2−·2H2O, the benzene rings of the 4,5,6-trihy­droxy­benzene-1,3-disulfonate ions, which are stacked parallel to each other forming rods parallel to the a axis, are slightly deformed (planarity, symmetry) mainly because of the high degree of substitution. The two sodium ions, located within pockets of the anion rods, are coordinated by six and seven O atoms, resulting in octa­hedral and penta­gonal-bipyramidal coordinations, respectively. In addition to these coordinative bonds towards sodium, an extended network of intra- and inter­molecular hydrogen bonds occurs. PMID:21587412

  11. Linking structure to function: Recent lessons from inositol 1,4,5-trisphosphate receptor mutagenesis.

    PubMed

    Yule, David I; Betzenhauser, Matthew J; Joseph, Suresh K

    2010-06-01

    Great insight has been gained into the structure and function of the inositol 1,4,5 trisphosphate receptor (InsP(3)R) by studies employing mutagenesis of the cDNA encoding the receptor. Notably, early studies using this approach defined the key constituents required for InsP(3) binding in the N-terminus and the membrane spanning regions in the C-terminal domain responsible for channel formation, targeting and function. In this article we evaluate recent studies which have used a similar approach to investigate key residues underlying the in vivo modulation by select regulatory factors. In addition, we review studies defining the structural requirements in the channel domain which comprise the conduction pathway and are suggested to be involved in the gating of the channel.

  12. Bis(imidazo[4,5-f][1,10]phenanthroline)dinitratolead(II)

    PubMed Central

    Li, Chun-Xiang; Zha, Xiao-Lin; Liu, Chun-Bo; Li, Xiu-Ying; Che, Guang-Bo

    2009-01-01

    In the title compound, [Pb(NO3)2(C13H8N4)2], the PbII atom (site symmetry 2) is hexa­coordinated by four N atoms from two N,N′-bidentate imidazo[4,5-f][1,10]phenanthroline (L) ligands and two O atoms from two weakly coordinated nitrate ions [Pb—O = 2.872 (5) Å] in an irregular arrangement, which may be ascribed to the stereochemically active lone pair of electrons on the metal ion. In the crystal, inter­molecular bifurcated N—H⋯(O,O) hydrogen bonds connect the mol­ecules into chains propagating along [100]. Adjacent chains inter­act by strong aromatic π–π stacking inter­actions, with a centroid–centroid distance of 3.483 (2) Å. PMID:21581524

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Rules for pluralization in African American English: Evidence from 4-, 5-, and 6-year-olds

    NASA Astrophysics Data System (ADS)

    Trent-Brown, Sonja A.

    2005-09-01

    This study investigated the African American English (AAE) forms produced by 4-, 5-, and 6-year-old children when pluralizing words ending in final consonant clusters. Participants were 105 child and 45 adult speakers of AAE. Speakers provided verbal responses to pictures of cartoon-like creatures with nonsense word names. Responses were recorded and presented to experienced listeners for language set and singular versus plural judgments. An acoustical analysis was conducted for comparison to the perceptual findings. Results suggest that although [s] inflection is nonobligatory in AAE, there are many instances in which it does occur. Variation in plural forms across final consonant clusters is discussed as well as other markers for pluralization in the absence of the [s] morpheme.

  1. 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…

  2. Primary torsion of the greater omentum.

    PubMed

    Aoki, Y; Oka, S; Nakamura, M; Nakatsuka, H; Yamade, N; Maeda, Y

    1991-11-01

    A case with primary torsion of the greater omentum is reported. This pathological condition is an uncommon cause of acute abdominal emergency and it is very difficult even for general surgeons to differentiate this from other acute abdomen. The etiology remains unknown and the treatment of choice is resection of the affected organ. PMID:1820017

  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. Phosphatidylinositol-4,5-bisphosphate regulates epidermal growth factor receptor activation

    PubMed Central

    Michailidis, Ioannis E.; Rusinova, Radda; Georgakopoulos, Anastasios; Chen, Yibang; Iyengar, Ravi; Robakis, Nikolaos K.; Logothetis, Diomedes E.; Baki, Lia

    2012-01-01

    Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2 or PIP2] is a direct modulator of a diverse array of proteins in eukaryotic cells. The functional integrity of transmembrane proteins, such as ion channels and transporters, is critically dependent on specific interactions with PIP2 and other phosphoinositides. Here, we report a novel requirement for PIP2 in the activation of the epidermal growth factor receptor (EGFR). Down-regulation of PIP2 levels either via pharmacological inhibition of PI kinase activity, or via manipulation of the levels of the lipid kinase PIP5K1α and the lipid phosphatase synaptojanin, reduced EGFR tyrosine phosphorylation, whereas up-regulation of PIP2 levels via overexpression of PIP5K1α had the opposite effect. A cluster of positively charged residues in the juxtamembrane domain (basic JD) of EGFR is likely to mediate binding of EGFR to PIP2 and PIP2-dependent regulation of EGFR activation. A peptide mimicking the EGFR juxtamembrane domain that was assayed by surface plasmon resonance displayed strong binding to PIP2. Neutralization of positively charged amino acids abolished EGFR/PIP2 interaction in the context of this peptide and down-regulated epidermal growth factor (EGF)-induced EGFR autophosphorylation and EGF-induced EGFR signaling to ion channels in the context of the full-length receptor. These results suggest that EGFR activation and downstream signaling depend on interactions of EGFR with PIP2 and point to the basic JD’s critical involvement in these interactions. The addition of this very different class of membrane proteins to ion channels and transporters suggests that PIP2 may serve as a general modulator of the activity of many diverse eukaryotic transmembrane proteins through their basic JDs. PMID:21107857

  5. 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.

  6. 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

  7. 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

  8. 600 ns pulse electric field-induced phosphatidylinositol4,5-bisphosphate depletion.

    PubMed

    Tolstykh, Gleb P; Beier, Hope T; Roth, Caleb C; Thompson, Gary L; Ibey, Bennett L

    2014-12-01

    The interaction between nsPEF-induced Ca(2+) release and nsPEF-induced phosphatidylinositol4,5-bisphosphate (PIP2) hydrolysis is not well understood. To better understand this interrelation we monitored intracellular calcium changes, in cells loaded with Calcium Green-1 AM, and generation of PIP2 hydrolysis byproducts (inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)) in cells transfected with one of two fluorescent reporter genes: PLCδ-PH-EGFP or GFP-C1-PKCγ-C1a. The percentage fluorescence differences (ΔF %) after exposures were determined. Upon nsPEF impact, we found that in the absence of extracellular Ca(2+) the population of IP3 liberated during nsPEF exposure (ΔF 6%±3, n=22), is diminished compared to the response in the presence of calcium (ΔF 84%±15, n=20). The production of DAG in the absence of extracellular Ca(2+) (ΔF 29%±5, n=25), as well as in cells exposed to thapsigargin (ΔF 40%±12, n=15), was not statistically different from cells exposed in the presence of extracellular calcium (ΔF 22±6%, n=18). This finding suggests that the change in intracellular calcium concentration is not solely driving the observed response. Interestingly, the DAG produced in the absence of Ca(2+) is the strongest near the membrane regions facing the electrodes, whereas the presence of extracellular Ca(2+) leads to a whole cell response. The reported observations of Ca(2+) dynamics combined with IP3 and DAG production suggest that nsPEF may cause a direct effect on the phospholipids within the plasma membrane.

  9. 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

  10. 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.

  11. 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.

  12. Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2.

    PubMed

    Höning, Stefan; Ricotta, Doris; Krauss, Michael; Späte, Kira; Spolaore, Barbara; Motley, Alison; Robinson, Margaret; Robinson, Carol; Haucke, Volker; Owen, David J

    2005-05-27

    The alpha,beta2,mu2,sigma2 heterotetrameric AP2 complex is recruited exclusively to the phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P(2))-rich plasma membrane where, amongst other roles, it selects motif-containing cargo proteins for incorporation into clathrin-coated vesicles. Unphosphorylated and mu2Thr156-monophosphorylated AP2 mutated in their alphaPtdIns4,5P(2), mu2PtdIns4,5P(2), and mu2Yxxvarphi binding sites were produced, and their interactions with membranes of different phospholipid and cargo composition were measured by surface plasmon resonance. We demonstrate that recognition of Yxxvarphi and acidic dileucine motifs is dependent on corecognition with PtdIns4,5P(2), explaining the selective recruitment of AP2 to the plasma membrane. The interaction of AP2 with PtdIns4,5P(2)/Yxxvarphi-containing membranes is two step: initial recruitment via the alphaPtdIns4,5P(2) site and then stabilization through the binding of mu2Yxxvarphi and mu2PtdIns4,5P(2) sites to their ligands. The second step is facilitated by a conformational change favored by mu2Thr156 phosphorylation. The binding of AP2 to acidic-dileucine motifs occurs at a different site from Yxxvarphi binding and is not enhanced by mu2Thr156 phosphorylation.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P(2) rafts.

    PubMed

    Caroni, P

    2001-08-15

    The phosphoinositide lipid PI(4,5)P(2) is now established as a key cofactor in signaling to the actin cytoskeleton and in vesicle trafficking. PI(4,5)P(2) accumulates at membrane rafts and promotes local co-recruitment and activation of specific signaling components at the cell membrane. PI(4,5)P(2) rafts may thus be platforms for local regulation of morphogenetic activity at the cell membrane. Raft PI(4,5)P(2) is regulated by lipid kinases (PI5-kinases) and lipid phosphatases (e.g. synaptojanin). In addition, GAP43-like proteins have recently emerged as a group of PI(4,5)P(2) raft-modulating proteins. These locally abundant proteins accumulate at inner leaflet plasmalemmal rafts where they bind to and co-distribute with PI(4,5)P(2), and promote actin cytoskeleton accumulation and dynamics. In keeping with their proposed role as positive modulators of PI(4,5)P(2) raft function, GAP43-like proteins confer competence for regulated morphogenetic activity on cells that express them. Their function has been investigated extensively in the nervous system, where their expression promotes neurite outgrowth, anatomical plasticity and nerve regeneration. Extrinsic signals and intrinsic factors may thus converge to modulate PI(4,5)P(2) rafts, upstream of regulated activity at the cell surface.

  19. 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.

  20. A Universal Role for Inositol 1,4,5-Trisphosphate-Mediated Signaling in Plant Gravitropism1[W

    PubMed Central

    Perera, Imara Y.; Hung, Chiu-Yueh; Brady, Shari; Muday, Gloria K.; Boss, Wendy F.

    2006-01-01

    Inositol 1,4,5-trisphosphate (InsP3) has been implicated in the early signaling events of plants linking gravity sensing to the initiation of the gravitropic response. However, at present, the contribution of the phosphoinositide signaling pathway in plant gravitropism is not well understood. To delineate the role of InsP3 in plant gravitropism, we generated Arabidopsis (Arabidopsis thaliana) plants constitutively expressing the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme that specifically hydrolyzes InsP3. The transgenic plants show no significant differences in growth and life cycle compared to wild-type plants, although basal InsP3 levels are reduced by greater than 90% compared to wild-type plants. With gravistimulation, InsP3 levels in inflorescence stems of transgenic plants show no detectable change, whereas in wild-type plant inflorescences, InsP3 levels increase approximately 3-fold within the first 5 to 15 min of gravistimulation, preceding visible bending. Furthermore, gravitropic bending of the roots, hypocotyls, and inflorescence stems of the InsP 5-ptase transgenic plants is reduced by approximately 30% compared with the wild type. Additionally, the cold memory response of the transgenic plants is attenuated, indicating that InsP3 contributes to gravisignaling in the cold. The transgenic roots were shown to have altered calcium sensitivity in controlling gravitropic response, a reduction in basipetal indole-3-acetic acid transport, and a delay in the asymmetric auxin-induced β-glucuronidase expression with gravistimulation as compared to the controls. The compromised gravitropic response in all the major axes of growth in the transgenic Arabidopsis plants reveals a universal role for InsP3 in the gravity signal transduction cascade of plants. PMID:16384898

  1. 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.

  2. GTP-dependent hydrolysis of phosphatidylinositol-4,5-bisphosphate by a soluble phospholipase C from adult human epidermis

    SciTech Connect

    Fisher, G.J.; Baldassare, J.J.; Voorhees, J.J.

    1987-05-01

    The effects of tumor promoting phorbol esters, which activate protein kinase (C (PK-C), on epidermis suggest that PK-C is important in the regulation of epidermal growth and differentiation. Since in vivo PK-C is activated by the products of phospholipase C (PL-C)-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP/sub 2/), they have investigated the properties of this reaction. Soluble PL-C from adult human epidermis was incubated with sonicated lipid vesicles containing (/sup 3/H-inositol)PIP/sub 2/, for 10 minutes at 37/sup 0/C. Water soluble reaction products were extracted, chromatographed and quantitated. In the presence of physiological concentrations of Ca/sup + +/ magnesium and GTP PIP/sub 2/, but not phosphatidylinositol, was hydrolyzed by PL-C (11.7 nmol/min/mg). Addition of GTP or GTP..gamma..S stimulated activity greater than 15 fold. Half maximal and maximal activity were observed at 10 ..mu..M and 100 ..mu..M GTP..gamma..S, respectively. ATP was unable to substitute for GTP, and GDP/S inhibited PIP/sub 2/ hydrolysis in a dose dependent manner. Activity was sensitive to pH, and exhibited a sharp optimum at pH 6.5. In addition, the PL-C preparation specifically bound (/sup 35/S)GTP S. These data demonstrate that adult human epidermis contains PL-C activity that specifically hydrolyzes PIP/sub 2/ and suggest the involvement of a GTP-binding regulatory protein in this reaction.

  3. 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

  4. 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...

  5. Environmental planning and management in Greater Johannesburg.

    PubMed

    Von Schirnding, Y E

    1996-03-01

    This article describes the actions among urban environmental, management, and development planners in Greater Johannesburg, South Africa. Initiatives, such as the Healthy Cities Project and Model Communities, are being integrated into an environmental management and development approach that attains the goals of Agenda 21. Greater Johannesburg has housing shortages and homelessness. Priority needs include the areas of housing, water, electricity, public transportation, and sanitation. Clean water and air are inequitably distributed. Other key environmental problems include illegal dumping, inadequate waste disposal, poor environmental hygiene in overcrowded inner city areas, lack of open spaces, flooding, and water scarcities. The newly formed metropolitan authority offers opportunities to improve coordination and integration of environmental problems. Stakeholders from government at all levels, politicians, nongovernmental organizations, and the business sector formed an intersectoral, interdepartmental environment management committee in 1995. Stakeholders will integrate Agenda 21 within broader urban development plans and processes. The executive committee and the full council approved a set of guiding principles on environmental policy and an administrative framework for management. Four workshops were held to ensure a participatory consultation process in 1995. The WHO Collaborating Center for Urban Health will be used to facilitate the work of the Greater Johannesburg Metropolitan Council. Changes are being made in the way local governments work.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Structural and Theoretical Investigation of Anhydrous 3,4,5-Triacetoxybenzoic Acid.

    PubMed

    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 [Formula: see text] space group (Z' = 1) and its packing shows a supramolecular motif in a classical [Formula: see text] 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

  14. Legionella phosphatase hydrolyzes phosphatidylinositol 4,5-bisphosphate and inosital triphosphate in human neutrophils

    SciTech Connect

    Dowling, J.N.; Saha, A.K.; Glew, R.H.

    1987-05-01

    Legionella are facultative intracellular bacterial pathogens which multiply in host phagocytes. L. micdadei cells contain an acid phosphatase (ACP) that blocks superoxide anion production by human neutrophils stimulated with the formylated peptide, fMLP. The possibility that ACP acts by interefering with polyphosphoinositide metabolism and the production of the intracellular second messenger, inositol triphosphate (IP3) was explored. When neutrophil phosphoinositides were labeled with TSP, incubation of the cells with ACP caused an 85% loss of the labeled phosphatidylinositol-4,5-bisphosphate (PIP2) over 2 h. Treatment of (TH)inositol-labeled neutrophils with ACP for 30 min resulted in a 20% decrease of labeled PIP2. Following fMLP stimulation, the fractional reduction in PIP2 and the fractional increase in IP3 was the same in ACP-treated and untreated neutrophils, but the total quantity of IP3 was reduced by ACP pre-treatment. The reduction in IP3 generated following fMLP stimulation seems to be due primarily to the decreased amount of PIP2 available for hydrolysis. However, some loss of IP3 due to direct hydrolysis by ACP cannot be ruled out. The Legionella phosphatase may compromise neutrophil response to the bacteria by hydrolyzing PIP2, the prognitor of IP3, and by hydrolyzing IP3 itself.

  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 L; 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. 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

  17. Pentaleno[1,2-a:4,5']diacenaphthylenes: Uniquely Stabilized Pentalene Derivatives.

    PubMed

    Yuan, Bingxin; Zhuang, Junpeng; Kirmess, Kristopher M; Bridgmohan, Chelsea N; Whalley, Adam C; Wang, Lichang; Plunkett, Kyle N

    2016-09-16

    We demonstrate the preparation of diacenaphthopentalene derivatives via a palladium-catalyzed dimerization of 1-iodo-2-arylethynyl-acenaphthylenes. The resulting 7,14-diarylpentaleno[1,2-a:4,5a']diacenaphthylenes, which contain four linearly fused five-membered rings, are benchtop stable and behave as hole-transporting or ambipolar semiconductors in organic field effect transistors. The X-ray crystal structure shows the important role of the fused naphthalene unit that enforces a formal pentalene subunit at the central five-membered rings and [5]-radialene-like structures at the proximal five-membered rings. Nucleus-independent chemical shift (NICS) calculations show the internal pentalene rings are intermediate in antiaromaticity character between known pentalene and dibenzopentalenes derivatives. The diacenaphthopentalene derivatives give high optical gap materials owing to a forbidden HOMO to LUMO transition, yet have narrow electrochemical gaps and are reduced at small negative potentials giving LUMO energy levels of -3.57 to -3.74 eV. PMID:27559925

  18. 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

  19. 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.

  20. Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration

    PubMed Central

    Lee, Bora; Lee, Seung-Min; Bahn, Young Jae; Lee, Kwang-Pyo; Kang, Moonkyung; Kim, Yeon-Soo; Woo, Sun-Hee; Lim, Jae-Young; Kim, Eunhee; Kwon, Ki-Sun

    2016-01-01

    Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID:27658230

  1. Reduction of carcinogenic 4(5)-methylimidazole in a caramel model system: influence of food additives.

    PubMed

    Seo, Seulgi; Ka, Mi-Hyun; Lee, Kwang-Geun

    2014-07-01

    The effect of various food additives on the formation of carcinogenic 4(5)-methylimidazole (4-MI) in a caramel model system was investigated. The relationship between the levels of 4-MI and various pyrazines was studied. When glucose and ammonium hydroxide were heated, the amount of 4-MI was 556 ± 1.3 μg/mL, which increased to 583 ± 2.6 μg/mL by the addition of 0.1 M of sodium sulfite. When various food additives, such as 0.1 M of iron sulfate, magnesium sulfate, zinc sulfate, tryptophan, and cysteine were added, the amount of 4-MI was reduced to 110 ± 0.7, 483 ± 2.0, 460 ± 2.0, 409 ± 4.4, and 397 ± 1.7 μg/mL, respectively. The greatest reduction, 80%, occurred with the addition of iron sulfate. Among the 12 pyrazines, 2-ethyl-6-methylpyrazine with 4-MI showed the highest correlation (r = -0.8239).

  2. 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

  3. Direct and selective elimination of specific prions and amyloids by 4,5-dianilinophthalimide and analogs

    PubMed Central

    Wang, Huan; Duennwald, Martin L.; Roberts, Blake E.; Rozeboom, Leslie M.; Zhang, Yingxin L.; Steele, Andrew D.; Krishnan, Rajaraman; Su, Linhui Julie; Griffin, Drees; Mukhopadhyay, Samrat; Hennessy, Edward J.; Weigele, Peter; Blanchard, Barbara J.; King, Jonathan; Deniz, Ashok A.; Buchwald, Stephen L.; Ingram, Vernon M.; Lindquist, Susan; Shorter, James

    2008-01-01

    Mechanisms to safely eliminate amyloids and preamyloid oligomers associated with many devastating diseases are urgently needed. Biophysical principles dictate that small molecules are unlikely to perturb large intermolecular protein–protein interfaces, let alone extraordinarily stable amyloid interfaces. Yet 4,5-dianilinophthalimide (DAPH-1) reverses Aβ42 amyloidogenesis and neurotoxicity, which is associated with Alzheimer's disease. Here, we show that DAPH-1 and select derivatives are ineffective against several amyloidogenic proteins, including tau, α-synuclein, Ure2, and PrP, but antagonize the yeast prion protein, Sup35, in vitro and in vivo. This allowed us to exploit several powerful new tools created for studying the conformational transitions of Sup35 and decipher the mechanisms by which DAPH-1 and related compounds antagonize the prion state. During fibrillization, inhibitory DAPHs alter the folding of Sup35's amyloidogenic core, preventing amyloidogenic oligomerization and specific recognition events that nucleate prion assembly. Select DAPHs also are capable of attacking preformed amyloids. They remodel Sup35 prion-specific intermolecular interfaces to create morphologically altered aggregates with diminished infectivity and self-templating activity. Our studies provide mechanistic insights and reinvigorate hopes for small-molecule therapies that specifically disrupt intermolecular amyloid contacts. PMID:18480256

  4. 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).

  5. Role of inositol 1,4,5-triphosphate signalling in gravitropic and phototropic gene expression.

    PubMed

    Salinas-Mondragon, Raul E; Kajla, Jyoti D; Perera, Imara Y; Brown, Christopher S; Sederoff, Heike Winter

    2010-12-01

    Plants sense light and gravity to orient their direction of growth. One common component in the early events of both phototropic and gravitropic signal transduction is activation of phospholipase C (PLC), which leads to an increase in inositol 1,4,5-triphosphate (InsP(3)) levels. The InsP(3) signal is terminated by hydrolysis of InsP(3) through inositolpolyphosphate-5-phosphatases (InsP 5-ptases). Arabidopsis plants expressing a heterologous InsP 5-ptase have low basal InsP(3) levels and exhibit reduced gravitropic and phototropic bending. Downstream effects of InsP(3)-mediated signalling are not understood. We used comparative transcript profiling to characterize gene expression changes in gravity- or light-stimulated Arabidopsis root apices that were manipulated in their InsP(3) metabolism either through inhibition of PLC activity or expression of InsP 5-ptase. We identified InsP(3)-dependent and InsP(3)-independent co-regulated gene sets in response to gravity or light stimulation. Inhibition of PLC activity in wild-type plants caused similar changes in transcript abundance in response to gravitropic and phototropic stimulation as in the transgenic lines. Therefore, we conclude that changes in gene expression in response to gravitropic and phototropic stimulation are mediated by two signal transduction pathways that vary in their dependence on changes in InsP(3).

  6. 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.

  7. Phase transformations in Ti-6.8Mo-4.5Fe-1.5Al

    SciTech Connect

    Azimzadeh, S.; Rack, H.J.

    1998-10-01

    Phase transformations during artificial and isothermal aging of Ti-6.8Mo-4.5Fe-1.5Al have been investigated over the temperature range from 300 C to 750 C utilizing hardness measurements, X-ray diffraction, optical microscopy, and electron microscopy. Artificial aging following solution treatment and water quenching initially involved growth of the athermal {omega} phase. This was followed by formation of the {alpha} phase, either in association with the {omega} phase, through homogeneous precipitation within the matrix, or through heterogeneous grain-boundary nucleation. Similarly, isothermal decomposition of the metastable {beta} phase resulted in the precipitation of {omega} phase exhibiting an ellipsoidal morphology. While precipitation of {omega} was immediate at 345 C, an incubation period was observed upon aging at 390 C. Isothermal aging above this temperature involved direct precipitation of the {alpha} phase, either homogeneously within the {beta} matrix or heterogeneously at {beta} grain boundaries. The extent of homogeneous vs heterogeneous {alpha} nucleation during isothermal aging depended upon aging temperature; low aging temperatures promote homogeneous nucleation and higher aging temperatures promote {alpha} heterogeneous nucleation. Finally, continued aging resulted, independent of aging path, in coarsening and spheroidization of the {alpha} phase.

  8. Ensemble perception of size in 4-5-year-old children.

    PubMed

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

    2015-07-01

    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 ensemble coding to perceive the average size of a group of objects. Children viewed a pair of trees, with each containing a group of differently sized oranges. We found that, in order to determine which tree had the larger oranges overall, children integrated the sizes of multiple oranges into ensemble representations. This pooling occurred rapidly, and it occurred despite conflicting information from numerosity, continuous extent, density, and contrast. An ideal observer analysis showed that although children's integration mechanisms are sensitive, they are not yet as efficient as adults'. Overall, our results provide a new insight into the way children see and understand the environment, and they illustrate the fundamental nature of ensemble coding in visual perception.

  9. Novel Phosphotidylinositol 4,5-Bisphosphate Binding Sites on Focal Adhesion Kinase

    PubMed Central

    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

  10. 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.

  11. A study of perceptual and verbal skills of disabled readers in grades 4, 5 and 6.

    PubMed

    Solan, H A; Ficarra, A P

    1990-08-01

    This investigation addresses the role of the optometrist in diagnosing and treating children in grades 4, 5, and 6 who have been identified as reading disabled. Fifty-one subjects with average intelligence, but whose reading comprehension skills were below the 31st percentile (mean, 20th percentile), were evaluated using verbal and perceptual tests. When the performance of this experimental group was compared with the mean scores from standardized test norms for each of the various tasks, the disabled readers scored significantly lower in seven of the eight perceptual and five of the six verbal tasks. These results lend support to the hypothesis that both perceptual and verbal deficits are related to reading comprehension. Using step-wise multiple correlation analysis, three perceptual factors; eye-movements, Auditory-Visual Integration Test (AVIT), and grooved peg-board, contributed 38 percent of the variance whereas the addition of two verbal factors (digit span and token test) provided just 2 percent. That is, 38 percent of the variations in reading comprehension could be accounted for by variations in perceptual skills in the disabled readers. The results were interpreted in terms of spatial-simultaneous and verbal-successive processing skills.

  12. Theoretical Investigation on Mechanistic and Kinetic Transformation of 2,2',4,4',5-Pentabromodiphenyl Ether.

    PubMed

    Cao, Haijie; Han, Dandan; Li, Mingyue; Li, Xin; He, Maoxia; Wang, Wenxing

    2015-06-18

    This study investigates the decomposition of 2,2',4,4',5-pentabrominated diphenyl ether (BDE99), a commonly detected pollutant in the environment. Debromination channels yielding tetrabrominated diphenyl ethers and hydrogen abstracting aromatic bromine atom formations play significant roles in the reaction of BDE99 + H, in which the former absolutely predominates bimolecular reactions. Polybrominated dibenzo-p-dioxins (PBDDs) and polybrominated dibenzofurans (PBDFs) can be produced during BDE99 pyrolysis, especially for PBDFs under inert conditions. The expected dominant pathways in a closed system are debromination products and PBDF formations. The bimolecular reaction with hydroxyl radical mainly leads to hydroxylated BDE99s rather than hydroxylated tetrabrominated diphenyl ethers. PBDDs are then generated from ortho-hydroxylated PBDEs. HO2 radical reactions rarely proceed. The total rate constants for the BDE99 reaction with hydrogen atoms and hydroxyl radicals exhibit positive dependence on temperature with values of 1.86 × 10(-14) and 5.24 × 10(-14) cm(3) molecule(-1) s(-1) at 298.15 K, respectively.

  13. Optimization and In Vivo Toxicity Evaluation of G4.5 Pamam Dendrimer-Risperidone Complexes

    PubMed Central

    Prieto, Maria Jimena; del Rio Zabala, Nahuel Eduardo; Marotta, Cristian Hernán; Carreño Gutierrez, Hector; Arévalo Arévalo, Rosario; Chiaramoni, Nadia Silvia; Alonso, Silvia del Valle

    2014-01-01

    Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex. PMID:24587349

  14. Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

    PubMed

    Prieto, Maria Jimena; del Rio Zabala, Nahuel Eduardo; Marotta, Cristian Hernán; Carreño Gutierrez, Hector; Arévalo Arévalo, Rosario; Chiaramoni, Nadia Silvia; del Valle Alonso, Silvia

    2014-01-01

    Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex. PMID:24587349

  15. 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

  16. 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.

  17. 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.

  18. PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility.

    PubMed

    Golub, Tamara; Caroni, Pico

    2005-04-11

    The lipid second messenger PI(4,5)P(2) modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P(2)-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promoting cell surface motility, PI(4,5)P(2) directs the assembly of dynamic raft-rich plasmalemmal patches, which promote and sustain protrusive motility. The accumulation of PI(4,5)P(2) at rafts, together with Cdc42, promotes patch assembly through N-WASP. The patches exhibit locally regulated PI(4,5)P(2) turnover and reduced diffusion-mediated exchange with their environment. Patches capture microtubules (MTs) through patch IQGAP1, to stabilize MTs at the leading edge. Captured MTs in turn deliver PKA to patches to promote patch clustering through further PI(4,5)P(2) accumulation in response to cAMP. Patch clustering restricts, spatially confines, and polarizes protrusive motility. Thus, PI(4,5)P(2)-dependent raft-rich patches enhance local signaling for motility, and their assembly into clusters is regulated through captured MTs and PKA, coupling local regulation of motility to cell polarity, and organization.

  19. 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.

  20. Hospital design to support greater operating efficiency.

    PubMed

    Skaggs, R L

    1984-12-01

    With the new imperative on cost containment and particular emphasis on prospective payment, hospital design must support greater productivity. It is incumbent on architects and engineers to reduce construction costs; but more importantly, to design facilities that improve personnel productivity. Several approaches to designing for efficiency are discussed including improving the development process; systems building, ease of maintenance, and conserving energy; developing the model hospital; minimizing travel throughout the hospital; centralization vs. decentralization; automating support systems; designing for growth and change; analyzing workflow; utilizing swing space; and emphasizing consumer centered care.

  1. 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.

  2. 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

  3. Highly stereoselective construction of spiro[4.5]decanes by SmI(2)-promoted ketyl radical mediated tandem cyclization.

    PubMed

    Inui, Masaharu; Nakazaki, Atsuo; Kobayashi, Susumu

    2007-02-01

    [reaction: see text] Ketyl radical mediated tandem cyclization of omega-alkynyl carbonyl compounds bearing activated alkene using SmI(2) gave spiro[4.5]decanes stereoselectively. In the presence of HMPA, alpha,beta-unsaturated esters and alkenyl phosphonates were converted to spiro[4.5]decanes and a monocyclic compound, respectively. In the presence of Sm, bicyclic lactones were obtained from alpha,beta-unsaturated esters. The spiro[4.5]decane was provided from an alkenyl phosphonate. Interestingly, the stereochemical changeover at the first cyclization has been controlled by means of a variety of activators.

  4. Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Analogues of IP3

    PubMed Central

    Saleem, Huma; Tovey, Stephen C.; Rahman, Taufiq; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

    2013-01-01

    Most animal cells express mixtures of the three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R) encoded by vertebrate genomes. Activation of each subtype by different agonists has not hitherto been examined in cells expressing defined homogenous populations of IP3R. Here we measure Ca2+ release evoked by synthetic analogues of IP3 using a Ca2+ indicator within the lumen of the endoplasmic reticulum of permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R. Phosphorylation of (1,4,5)IP3 to (1,3,4,5)IP4 reduced potency by ∼100-fold. Relative to (1,4,5)IP3, the potencies of IP3 analogues modified at the 1-position (malachite green (1,4,5)IP3), 2-position (2-deoxy(1,4,5)IP3) or 3-position (3-deoxy(1,4,5)IP3, (1,3,4,5)IP4) were similar for each IP3R subtype. The potency of an analogue, (1,4,6)IP3, in which the orientations of the 2- and 3-hydroxyl groups were inverted, was also reduced similarly for all three IP3R subtypes. Most analogues of IP3 interact similarly with the three IP3R subtypes, but the decrease in potency accompanying removal of the 1-phosphate from (1,4,5)IP3 was least for IP3R3. Addition of a large chromophore (malachite green) to the 1-phosphate of (1,4,5)IP3 only modestly reduced potency suggesting that similar analogues could be used to measure (1,4,5)IP3 binding optically. These data provide the first structure-activity analyses of key IP3 analogues using homogenous populations of each mammalian IP3R subtype. They demonstrate broadly similar structure-activity relationships for all mammalian IP3R subtypes and establish the potential utility of (1,4,5)IP3 analogues with chromophores attached to the 1-position. PMID:23372785

  5. 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

  6. Characteristics of Salmonella enterica serovar 4,[5],12:i:- as a monophasic variant of serovar Typhimurium.

    PubMed

    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.

  7. 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

  8. 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.

  9. METHANOL MASER EMISSION FROM GALACTIC CENTER SOURCES WITH EXCESS 4.5 {mu}m EMISSION

    SciTech Connect

    Chambers, E. T.; Yusef-Zadeh, F.; Roberts, D. E-mail: zadeh@northwestern.edu

    2011-05-20

    We present a study of signatures of on-going star formation in a sample of protostellar objects with enhanced 4.5 {mu}m emission ('green' sources) near the Galactic center. To understand how star formation in the Galactic center region compares to that of the Galactic disk, we used the Expanded Very Large Array to observe radiatively excited Class II 6.7 GHz CH{sub 3}OH masers and collisionally excited Class I 44 GHz CH{sub 3}OH masers, both tracers of high-mass star formation, toward a sample of 34 Galactic center and foreground 'green' sources. We find that 33% {+-} 15% of Galactic center sources are coincident with 6.7 GHz masers, and that 44% {+-} 17% of foreground sources are coincident with 6.7 GHz masers. For 44 GHz masers, we find correlation rates of 27% {+-} 13% and 25% {+-} 13% for Galactic center green sources and foreground green sources, respectively. Based on these CH{sub 3}OH maser detection rates, as well as correlations of green sources with other tracers of star formation, such as 24 {mu}m emission and infrared dark clouds (IRDCs), we find no significant difference between the green sources in the Galactic center and those foreground to it. This suggests that once the star formation process has begun, the environmental differences between the Galactic center region and the Galactic disk have little effect on its observational signatures. We do find, however, some evidence that may support a recent episode of star formation in the Galactic center region.

  10. 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.

  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. 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.

  13. 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.

  14. Functional inositol 1,4,5-trisphosphate receptors assembled from concatenated homo- and heteromeric subunits.

    PubMed

    Alzayady, Kamil J; Wagner, Larry E; Chandrasekhar, Rahul; Monteagudo, Alina; Godiska, Ronald; Tall, Gregory G; Joseph, Suresh K; Yule, David I

    2013-10-11

    Vertebrate genomes code for three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3). Individual IP3R monomers are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores. IP3R subtypes are regulated differentially by IP3, Ca(2+), ATP, and various other cellular factors and events. IP3R subtypes are seldom expressed in isolation in individual cell types, and cells often express different complements of IP3R subtypes. When multiple subtypes of IP3R are co-expressed, the subunit composition of channels cannot be specifically defined. Thus, how the subunit composition of heterotetrameric IP3R channels contributes to shaping the spatio-temporal properties of IP3-mediated Ca(2+) signals has been difficult to evaluate. To address this question, we created concatenated IP3R linked by short flexible linkers. Dimeric constructs were expressed in DT40-3KO cells, an IP3R null cell line. The dimeric proteins were localized to membranes, ran as intact dimeric proteins on SDS-PAGE, and migrated as an ∼1100-kDa band on blue native gels exactly as wild type IP3R. Importantly, IP3R channels formed from concatenated dimers were fully functional as indicated by agonist-induced Ca(2+) release. Using single channel "on-nucleus" patch clamp, the channels assembled from homodimers were essentially indistinguishable from those formed by the wild type receptor. However, the activity of channels formed from concatenated IP3R1 and IP3R2 heterodimers was dominated by IP3R2 in terms of the characteristics of regulation by ATP. These studies provide the first insight into the regulation of heterotetrameric IP3R of defined composition. Importantly, the results indicate that the properties of these channels are not simply a blend of those of the constituent IP3R monomers.

  15. 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.

  16. Formation of 4(5)-Methylimidazole in Aqueous d-Glucose-Amino Acids Model System.

    PubMed

    Karim, Faris; Smith, J Scott

    2016-01-01

    The International Agency for Research on Cancer (IRAC) has classified 4(5)-methylimidazole (4-MeI) as a group 2B possible human carcinogen. Thus, how 4-MeI forms in a D-glucose (Glu) amino acids (AA) model system is important, as it is how browning is affected. An aqueous solution of Glu was mixed individually in equimolar amounts at 3 concentrations (0.05, 0.1, and 0.15 M) with aqueous solutions of L-Alanine (Ala), L-Arginine (Arg), Glycine (Gly), L-Lysine (Lys), and L-Serine (Ser). The Glu-AA mixtures were reacted at 60, 120, and 160 °C for 1 h. The 4-MeI levels were measured by gas chromatography-mass spectrometry after derivatization with isobutylchloroformate. No 4-MeI was formed at 60 °C for any treatment combination; however, at 120 °C and 0.05 M, Glu-Arg and Glu-Lys produced 0.13 and 0.14 mg/kg of 4-MeI. At 160 °C and 0.05 M all treatment combinations formed 4-MeI. At 160 °C and 0.15 M, the observed levels of Glu-Ala, Glu-Arg, Glu-Gly, Glu-Lys, and Glu-Ser were 0.21, 1.00, 0.15, 0.22, and 0.16 mg/kg. The AA type, reactant concentrations, and temperature significantly affected (P < 0.001) formation of 4-MeI as well as browning. Glu-Lys treatment in all combinations produced the most browning, but Glu-Arg produced the most 4-MeI. This method showed that foods processed using low temperatures may have reduced levels of 4-MeI.

  17. Hydrogen peroxide down-regulates inositol 1,4,5-trisphosphate receptor content through proteasome activation.

    PubMed

    Martín-Garrido, A; Boyano-Adánez, M C; Alique, M; Calleros, L; Serrano, I; Griera, M; Rodríguez-Puyol, D; Griendling, K K; Rodríguez-Puyol, M

    2009-11-15

    Hydrogen peroxide (H(2)O(2)) is implicated in the regulation of signaling pathways leading to changes in vascular smooth muscle function. Contractile effects produced by H(2)O(2) are due to the phosphorylation of myosin light chain kinase triggered by increases in intracellular calcium (Ca(2+)) from intracellular stores or influx of extracellular Ca(2+). One mechanism for mobilizing such stores involves the phosphoinositide pathway. Inositol 1,4,5-trisphosphate (IP(3)) mobilizes intracellular Ca(2+) by binding to a family of receptors (IP(3)Rs) on the endoplasmic-sarcoplasmic reticulum that act as ligand-gated Ca(2+) channels. IP(3)Rs can be rapidly ubiquitinated and degraded by the proteasome, causing a decrease in cellular IP(3)R content. In this study we show that IP(3)R(1) and IP(3)R(3) are down-regulated when vascular smooth muscle cells (VSMC) are stimulated by H(2)O(2), through an increase in proteasome activity. Moreover, we demonstrate that the decrease in IP(3)R by H(2)O(2) is accompanied by a reduction in calcium efflux induced by IP(3) in VSMC. Also, we observed that angiotensin II (ANGII) induces a decrease in IP(3)R by activation of NADPH oxidase and that preincubation with H(2)O(2) decreases ANGII-mediated calcium efflux and planar cell surface area in VSMC. The decreased IP(3) receptor content observed in cells was also found in aortic rings, which exhibited a decreased ANGII-dependent contraction after treatment with H(2)O(2). Altogether, these results suggest that H(2)O(2) mediates IP(3)R down-regulation via proteasome activity.

  18. Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis.

    PubMed

    Son, Aran; Kim, Min Seuk; Jo, Hae; Byun, Hae Mi; Shin, Dong Min

    2012-02-01

    The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca(2+) signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP(3)) and IP(3)-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP(3) and evaluated IP(3)-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca(2+) signaling proteins such as IP(3) receptors (IP(3)Rs), plasma membrane Ca(2+) ATPase, and sarco/endoplasmic reticulum Ca(2+) ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP(3) was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP(3) levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP(3)Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP(3)Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP(3) levels and the IP(3)-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.

  19. Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival.

    PubMed

    Ivanova, Hristina; Vervliet, Tim; Missiaen, Ludwig; Parys, Jan B; De Smedt, Humbert; Bultynck, Geert

    2014-10-01

    Cell-death and -survival decisions are critically controlled by intracellular Ca(2+) homeostasis and dynamics at the level of the endoplasmic reticulum (ER). Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) play a pivotal role in these processes by mediating Ca(2+) flux from the ER into the cytosol and mitochondria. Hence, it is clear that many pro-survival and pro-death signaling pathways and proteins affect Ca(2+) signaling by directly targeting IP3R channels, which can happen in an IP3R-isoform-dependent manner. In this review, we will focus on how the different IP3R isoforms (IP3R1, IP3R2 and IP3R3) control cell death and survival. First, we will present an overview of the isoform-specific regulation of IP3Rs by cellular factors like IP3, Ca(2+), Ca(2+)-binding proteins, adenosine triphosphate (ATP), thiol modification, phosphorylation and interacting proteins, and of IP3R-isoform specific expression patterns. Second, we will discuss the role of the ER as a Ca(2+) store in cell death and survival and how IP3Rs and pro-survival/pro-death proteins can modulate the basal ER Ca(2+) leak. Third, we will review the regulation of the Ca(2+)-flux properties of the IP3R isoforms by the ER-resident and by the cytoplasmic proteins involved in cell death and survival as well as by redox regulation. Hence, we aim to highlight the specific roles of the various IP3R isoforms in cell-death and -survival signaling. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.

  20. Some properties of YBamCu1+mOy(m = 2, 3, 4, 5) superconductors

    NASA Astrophysics Data System (ADS)

    Chainok, Piyamas; Khuntak, Thanarat; Sujinnapram, Supphadate; Tiyasri, Somporn; Wongphakdee, Wirat; Kruaehong, Thitipong; Nilkamjon, Tunyanop; Ratreng, Sermsuk; Udomsamuthirun, Pongkaew

    2015-02-01

    We synthesized the YBamCu1+mOy superconductors; m = 2, 3, 4, 5 that were Y123 (YBa2 Cu3O7-x), Y134 (YBa3Cu4O9-x), Y145 (YBa4Cu5O11-x), Y156 (YBa5Cu6O13-x), by solid state reaction with the Y2O3, BaCO3 and CuO as the beginning materials. The calcination temperature was 950°C and varied the sintering temperature to be 950°C and 980°C. The resistivity measurement by four-point-probe technique showed that the Tconset of Y123, Y134, Y145, Y156 were at 97, 93, 91, 85 K, respectively. The XRD and Rietveld full-profile analysis method were used and found that the crystal structure was in the orthorhombic with Pmmm space group with the ratio c/a were 3.0, 4.0, 5.0 and 6.0 for Y123, Y134, Y145 and Y156, respectively. The oxygen content was characterized by Iodometric titration. The (Cu3+/Cu2+ and Oxygen content) were (0.28, 6.83), (0.19, 8.81), (0.13, 10.79), (0.16, 12.92) of Y123, Y134, Y145, Y156, respectively. We also found that the increasing of sintering temperature has reduced the oxygen content and the critical temperature of all samples.

  1. 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

  2. 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.

  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. 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.

  5. Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis

    PubMed Central

    Son, Aran; Kim, Min Seuk; Jo, Hae; Byun, Hae Mi

    2012-01-01

    The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca2+ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP3) and IP3-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP3 and evaluated IP3-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca2+ signaling proteins such as IP3 receptors (IP3Rs), plasma membrane Ca2+ ATPase, and sarco/endoplasmic reticulum Ca2+ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP3 was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP3 levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP3Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP3Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP3 levels and the IP3-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis. PMID:22416217

  6. 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

  7. Greater Influence of Aerosol on Cloud Microphysics

    NASA Astrophysics Data System (ADS)

    Jha, V.; Hudson, J. G.; Noble, S.

    2009-12-01

    CCN and cloud microphysics measurements are presented from four projects: RICO, PASE,ICE-L and POST. Correlations coefficients (R) between 1% supersaturation CCN concentrations and total cloud droplet concentrations were 0.80 in all four projects and for the combined data. R between CCN and larger cloud droplet concentrations progressively decreased with increasing sizes (Fig. 1A). At ~20 µm R was maximum negative and then reversed to smaller negative and even positive at larger drop sizes. R is positive for CCN with total cloud droplets because droplets are proportional to the concentrations of nuclei that they condensed upon, CCN. The negative R for CCN with larger droplets is due to competition among droplets for condensate. Competition for condensate is greater when CCN concentrations are higher and this limits droplet sizes, more so for higher concentrations. Negative R ensues because this reduces droplet concentrations above specific sizes to a greater extent for higher CCN concentrations. The greatest negative R thus occurs at the size range where droplet concentrations are the largest, the mode of the droplet size distributions. In Fig. 1 this is just beyond the average mode. At larger sizes droplet concentrations are lower (Fig. 1B) and thus there is less competition for condensate. The more numerous small sized droplets do not have enough surface area to affect the growth of the larger less numerous droplets. Thus at larger sizes with reduced competition, droplet concentrations are again proportional to the concentrations of the nuclei that they condensed upon. Often particle concentrations at various sizes are proportional. When this is the case there will be a positive R for CCN at 1% with such larger droplet concentrations such as PASE in Fig. 1A. Thus there are two directly conflicting influences on R; the usual positive R between CCN and droplets and the negative R due to competition for condensate. Thus lower R between CCN and droplet

  8. Characterization of recombinant Beta vulgaris 4,5-DOPA-extradiol-dioxygenase active in the biosynthesis of betalains.

    PubMed

    Gandía-Herrero, Fernando; García-Carmona, Francisco

    2012-07-01

    Betalains are water-soluble pigments with high antiradical capacity which bestow bright colors to flowers, fruits and other parts of most plants of the order Caryophyllales. The formation of the structural unit of all betalains, betalamic acid from the precursor amino acid 4,5-dihydroxyphenylalanine is catalyzed by the enzyme 4,5-DOPA-extradiol-dioxygenase followed by intramolecular cyclization of the 4,5-secodopa intermediate. This paper describes the purification and the molecular and functional characterization of an active 4,5-DOPA-extradiol-dioxygenase from the best-known source of betalains-Beta vulgaris-after heterologous expression in Escherichia coli. The enzyme is a monomeric protein with a molecular mass of 32 kDa characterized by chromatography, electrophoresis and MALDI-TOF analysis. Enzyme kinetic properties are characterized in the production of betalamic acid, the structural, chromophoric and bioactive unit of plant pigment betalains.

  9. 2D-t modeling of pulsed-2f-CCP in CF_4(5%)/Ar for oxide etching

    NASA Astrophysics Data System (ADS)

    Washio, G.; Maeshige, K.; Nakano, N.; Makabe, T.

    2000-10-01

    Capacitively coupled plasma (CCP) source with different frequency source at each of parallel plate electrodes is a powerful tool for doing etching. A time modulation of CCP by a pulsed-power operation may be one of the practical solution of the development of the charging free plasma process for etching. Then, (very) high frequency (VHF) power source is operated in a pulse mode, although the opposite bias electrode with patterned wafer is in cw operation at low frequency (LF). In this study, modeling has been performed in order to investigate the fluxed of positive and negative ions, and electrons to the wafer surface as a function of frequency (13.56 MHz, 100 MHz), amplitude and on/off period of the (V)HF source, as well as the amplitude of the LF (678 kHz) bias voltage at 50 mTorr in CF_4(5%)/Ar. We employed the RCT model, and also a hybrid model(E.Shidoji, N.Nakano, T.Makabe, Thin Solid Films 351 (1999) 37-41) consisting of Monte Carlo particle model of fast electrons and the RCT model. In particular, we discuss the rule of negative ions on the wafer surface during off-period in CF_4/Ar system with dissociative electron attachment at finite electron energy without thermal attachment.

  10. 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.

  11. The Spitzer/IRAC 4.5 micron full-orbit phase curve of the hot Jupiter HD 209458b

    NASA Astrophysics Data System (ADS)

    Zellem, R.; Lewis, N. K.; Knutson, H. A.; Griffith, C. A.; Fortney, J. J.; Showman, A. P.; Cowan, N. B.; Agol, E.; Burrows, A.; Charbonneau, D.; Deming, D.; Laughlin, G.; Langton, J.

    2014-03-01

    The hot Jupiter HD 209458b is one of the most favorable targets for full-orbit phase curve observations, as it is one of the brightest systems (V-mag = 7.65, K-mag = 6.308), has a large planet-to-star contrast, and offers a high signal-to-noise ratio and the ability to make highprecision measurements. This planet also serves as the archetype for a class of planets that have dayside temperature inversions; the differences between this class of planets and those lacking inversions (including HD 189733b) are currently not well-understood. Here we present the first full-orbit phase curve of HD 209458b observed with the Spitzer/IRAC 4.5 micron photometric band. Our data, which includes one primary transit and two secondary eclipses, was reduced with a pixel-mapping method to get within 1.145 times the photon noise limit. We measure the brightness temperature of the observed phase curve. The results are modeled with radiative transfer models along with other primary transit and secondary eclipse data to determine the pressure level of the emissions. We then compare these results to predictions from global circulation models, including those where magnetic effects and thermal inversions are present in order to determine the effect that HD 209458b's dayside temperature inversion has on its atmospheric circulation and chemistry.

  12. The Spitzer/IRAC 4.5 micron full-orbit phase curve of the hot Jupiter HD 209458b

    NASA Astrophysics Data System (ADS)

    Zellem, Robert; Lewis, N.; Knutson, H.; Griffith, C. A.; Fortney, J. J.; Showman, A. P.; Cowan, N. B.; Agol, E.; Burrows, A. S.; Charbonneau, D.; Deming, D.; Laughlin, G. P.; Langton, J. S.

    2014-01-01

    The hot Jupiter HD 209458b is one of the most favorable targets for full-orbit phase curve observations, as it is one of the brightest systems (V-mag = 7.65, K-mag = 6.308), has a large planet-to-star contrast, and offers a high signal-to-noise ratio and the ability to make high-precision measurements. This planet also serves as the archetype for a class of planets that have dayside temperature inversions; the differences between this class of planets and those lacking inversions (including HD 189733b) are currently not well-understood. Here we present the first full-orbit phase curve of HD 209458b observed with the Spitzer/IRAC 4.5 micron photometric band. Our data, which includes one primary transit and two secondary eclipses, was reduced with a pixel-mapping method to get within 1.145 times the photon noise limit. We measure the brightness temperature of the observed phase curve. The results are modeled with radiative transfer models along with other primary transit and secondary eclipse data to determine the pressure level of the emissions. We then compare these results to predictions from global circulation models, including those where magnetic effects and thermal inversions are present in order to determine the effect that HD 209458b's dayside temperature inversion has on its atmospheric circulation and chemistry.

  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. 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.

  15. [Greater trochanteric pain syndrome of the hip].

    PubMed

    Haviv, Barak; Bronak, Shlomo; Thein, Rafael

    2014-02-01

    Lateral pain of the hip with point tenderness at the Greater Trochanter is a common musculoskeletal complaint. It is frequently diagnosed as trochanteric bursitis; however, this term is inaccurate because of evident non-inflammatory pathologies, particularly of the abductor tendons of the hip. It is important to differentiate this extra-articular source from an intra-articular or a lower back source of pain. Imaging is useful in cases of trauma, prolonged pain or uncertain diagnosis. Non-operative treatment that involves modifying activities, physiotherapy, analgesics, steroid injections and shock wave therapy is usually helpful. Nevertheless, despite the above treatments, about one third of the patients suffer from chronic pain and disability. These patients may be candidates for operative intervention. Currently, there are endoscopic surgical techniques for local decompression, bursectomy and suture of torn tendons similar to surgery used in the shoulder. PMID:24716427

  16. 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.

  17. 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.

  18. 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

  19. Metal-Free Oxidative Spirocyclization of Alkynes with Sulfonylhydrazides Leading to 3-Sulfonated Azaspiro[4,5]trienones.

    PubMed

    Wen, Jiangwei; Wei, Wei; Xue, Shengnan; Yang, Daoshan; Lou, Yu; Gao, Chaoyang; Wang, Hua

    2015-05-15

    A novel and direct oxidative spirocyclization of arylpropiolamides with sulfonylhydrazides leading to 3-sulfonated azaspiro[4,5]trienones has been developed under metal-free conditions. The reaction is performed in a tandem manner constituted by the sequential sulfonylation of alkynes, ipso-carbocyclization, dearomatization, hydration, and oxidation processes, providing a convenient and efficient approach to various sulfonated azaspiro[4,5] trienones of biological importance.

  20. Excitation of Low-frequency Waves in the Solar Wind by Newborn Interstellar Pickup Ions H+ and He+ as Seen by Voyager at 4.5 AU

    NASA Astrophysics Data System (ADS)

    Joyce, Colin J.; Smith, Charles W.; Isenberg, Philip A.; Murphy, Neil; Schwadron, Nathan A.

    2010-12-01

    We report the observation of a spectral enhancement in the magnetic field fluctuations measured by the MAG instrument on the Voyager 2 spacecraft during 4.5 hr on DOY 7, 1979 at a heliocentric radial position of 4.5 AU. This time period is contained within a solar wind rarefaction when the large-scale interplanetary magnetic field was nearly radial. The frequency range and polarization of the enhanced fluctuations are consistent with waves generated by newly ionized interstellar H+ and He+. We show sunward propagation of the waves via a cross-helicity analysis. We compare the observation with a theoretical model and find reasonable agreement given the model assumptions. This event is the first indication of pickup ion-generated waves seen at Voyager. It is also the first identification of pickup He+ waves by any spacecraft.

  1. 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

  2. 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

  3. 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).

  4. 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

  5. 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

  6. 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.

  7. [Phenotypic and molecular characteristics of Salmonella enterica serotype 1,4, [5] ,12:i:--a review].

    PubMed

    Yang, Xiaojuan; Wu, Qingping; Zhang, Jumei; Guo, Weipeng

    2014-11-01

    Salmonella enterica serotype 1, 4, [5 ], 12: i:- ( Salmonella 1, 4, [5], 12: i:-), an emerging serotype antigenically related to Salmonella Typhimurium (1,4, [5], 12 : i:1,2) but lacking the second phase flagellar antigen, has been frequently detected in many countries over the last 10 years. Nowadays it seems to be one of the major serotypes responsible for human salmonellosis cases worldwide. In addition, multidrug resistance is quite common in Salmonella 1, 4, [5],12:i:-, the two major clones (labelled as Spanish and European clones) show multidrug resistance to four or more unrelated classes of antimicrobials mediated by plasmids or chromosome. Some resistance determinants including bla(TEM), bla(CTX-M(-1), aac(3)-IV, aadA2, cmlA1, sul1, sul2, dfrA12, strA-strB, tet (A) and tet (B) have been found in these multidrug resistance strains. The genomic characterization of 1,4, [5] ,12:i:- isolates suggests that this serovar is likely to gather several clones or strains that have independently emerged from S. Typhimurium, and have changed through multiple independent events involving different clonal groups. In later study, emphasis should be paid on development of rapid and precise detection methods and study of pathogenic and resistance mechanisms of Salmonella 1,4, [5] ,12:i:-.

  8. 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

  9. 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

  10. Regulation of the Putative TRPV1t Salt Taste Receptor by Phosphatidylinositol 4, 5-Bisphosphate

    PubMed Central

    Phan, Tam-Hao T.; Ren, ZuoJun; Mummalaneni, Shobha; Melone, Pamela; Mahavadi, Sunila; Murthy, Karnam S.; DeSimone, John A.

    2010-01-01

    Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP2) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 × 10−6 M; a specific ENaC blocker) and resiniferatoxin (RTX; 0–10 × 10−6 M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic effect on the NaCl + Bz CT response, increasing the CT response between 0.25 × 10−6 and 1 × 10−6 M. At concentrations >1 × 10−6 M, RTX inhibited the CT response. An increase in PIP2 by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP2 (a short chain synthetic PIP2) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP2 by topical lingual application of phenylarsine oxide (a phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response, increased its sensitivity to RTX stimulation, and inhibited the desensitization of the CT response at RTX concentrations >1 × 10−6 M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP2. An increase in PIP2 enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine) stimuli. RTX produced the same increase in the Bz-insensitive Na+response when present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No effect of RTX was observed on CT responses in WT mice and rats in the presence of the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 × 10−6 M) or in TRPV1 KO mice. We conclude that PIP2 is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP2 seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste

  11. 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

  12. Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Li, Xiaofan; Anishkin, Andriy; Liu, Hansi; van Rossum, Damian B; Chintapalli, Sree V; Sassic, Jessica K; Gallegos, David; Pivaroff-Ward, Kendra; Jegla, Timothy

    2015-11-01

    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

  13. Thermal evolution of the Greater Himalaya, Garhwal, India

    NASA Astrophysics Data System (ADS)

    Hodges, K. V.; Silverberg, David Scott

    1988-06-01

    The hanging wall of the Main Central Thrust (MCT) in Garhwal, India (roughly 79°N-80°E; 30°N-31°N), exhibits an inverted metamorphic gradient: sillimanite ± potassium feldspar assemblages near the top of the hanging wall, or Greater Himalayan sequence, are underlain by kyanite grade rocks near the fault. Textural relationships in pelitic samples from the Alaknanda and Dhauli river valleys indicate that the "inversion" is the product of two distinct metamorphic events: an early Harrovian event (M1), which affected the entire Greater, Himalayan sequence and a later Buchan event (M2), the effects of which are most obvious in the upper part of the sequence. Rim thermobarometry, garnet inclusion thermobarometry, and thermodynamic modeling of garnet zoning reveal that the basal portions of the metamorphic sequence experienced peak M1 conditions of >900 K and >960 MPa (roughly 36 km depth) before following an "erosion controlled" uplift path (e.g., England and Richardson, 1977). M2 metamorphic temperatures in the upper part of the sequence also exceeded 900 K, but maximum pressures (317-523 MPa) indicate paleodepths of only 12-19 km. Calculated pressure-temperature paths indicate that M2 was characterized by temperature increases of >80 K and roughly 5 km of tectonic burial We attribute M1 to tectonic burial of the Greater Himalayan sequence during the early stages of India-Eurasia collision. We believe that the uplift and cooling path of the sequence was interrupted in late Oligocene(?) - Miocene time by a second burial and heating event (M2) related to thrust imbrications in southern Tibet. This burial was coincident with the generation of leucogranites, which are abundant near the top of the Greater Himalayan sequence but are virtually absent near the MCT. Field relations do not constrain whether the leucogranites were derived from some presently unexposed portion of the Greater Himalayan sequence and were injected at their present structural level, or were melted

  14. 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

  15. The Pleckstrin Homology Domain of Diacylglycerol Kinase η Strongly and Selectively Binds to Phosphatidylinositol 4,5-Bisphosphate.

    PubMed

    Kume, Aiko; Kawase, Koki; Komenoi, Suguru; Usuki, Takako; Takeshita, Ena; Sakai, Hiromichi; Sakane, Fumio

    2016-04-01

    Type II diacylglycerol kinase (DGK) isozymes (δ, η, and κ) have a pleckstrin homology domain (PH) at their N termini. Here, we investigated the lipid binding properties of the PHs of type II DGK isozymes using protein-lipid overlay and liposome binding assays. The PH of DGKη showed the most pronounced binding activity to phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P2) among the various glycero- and sphingolipids including PI 3,4,5-trisphosphate, PI 3,4-bisphosphate, PI 3-phosphate, PI 4-phosphate, and PI 5-phosphate. Moreover, the PI(4,5)P2binding activity of the DGKη-PH was significantly stronger than that of other type II DGK isozymes. Notably, compared with the PH of phospholipase C (PLC) δ1, which is generally utilized as a cellular PI(4,5)P2- probe, the DGKη-PH is equal to or superior than the PLCδ1-PH in terms of affinity and selectivity for PI(4,5)P2 Furthermore, in COS-7 cells, GFP-fused wild-type DGKη1 and its PH partly translocated from the cytoplasm to the plasma membrane where the PLCδ1-PH was co-localized in response to hyperosmotic stress in an inositol 5-phosphatase-sensitive manner, whereas a PH deletion mutant did not. Moreover, K74A and R85A mutants of DGKη-PH, which lack the conserved basic amino acids thought to ligate PI(4,5)P2, were indeed unable to bind to PI(4,5)P2and co-localize with the PLCδ1-PH even in osmotically shocked cells. Overexpression of wild-type DGKη1 enhanced EGF-dependent phosphorylation of ERK, whereas either K74A or R85A mutant did not. Taken together, these results indicate that the DGKη-PH preferentially interacts with PI(4,5)P2and has crucial roles in regulating the subcellular localization and physiological function of DGKη. Moreover, the DGKη-PH could serve as an excellent cellular sensor for PI(4,5)P2.

  16. 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

  17. 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.

  18. 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

  19. Water quality improvement plan for Greater Vancouver

    SciTech Connect

    Foellmi, S.N. . Environmental Div.); Neden, D.G. ); Dawson, R.N. )

    1993-10-01

    The Greater Vancouver Regional District commissioned an 18-month planning and predesign study to define the components in a comprehensive water and predesign study to define the components in a comprehensive water quality improvement plan for its 2,500-ML/d (660-mgd) system. The study included three primary tasks: (1) predesign of disinfection and corrosion control facilities, (2) a 12-month pilot testing program using parallel pilot plants at the Seymour and Capilano water supply reservoirs, and (3) planning for future filtration plants. The results of the study identified chlorine, ammonia, sulfur dioxide, soda ash, and carbon dioxide in a two-stage treatment approach as the recommended disinfection and corrosion control scheme for the low-pH, low-alkalinity water supplies. The pilot-plant studies confirmed that direct filtration using deep-bed monomedium filters operating at a loading rate of 22.5 m/h provided excellent treatment performance and productivity over a wide range of raw-water quality. Ozonation was studied extensively and found not to be beneficial in the overall treatment performance. The phased improvement plan for the disinfection, corrosion control, and filtration facilities has an estimated capital cost of about Can$459 million.

  20. 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

  1. Nucleus-associated phosphorylation of Ins(1,4,5)P3 to InsP6 in Dictyostelium.

    PubMed Central

    Van der Kaay, J; Wesseling, J; Van Haastert, P J

    1995-01-01

    Although many cells contain large amounts of InsP6, its metabolism and function is still largely unknown. In Dictyostelium lysates, the formation of InsP6 by sequential phosphorylation of inositol via Ins(3,4,6)P3 has been described [Stevens and Irvine (1990) Nature (London) 346, 580-583]; the second messenger Ins(1,4,5)P3 was excluded as a potential substrate or intermediate for InsP6 formation. However, we observed that mutant cells labelled in vivo with [3H]inositol showed altered labelling of both [3H]Ins(1,4,5)P3 and [3H]InsP6. In this report we demonstrate that Ins(1,4,5)P3 is converted into InsP6 in vitro by nucleus-associated enzymes, in addition to the previously described stepwise phosphorylation of inositol to InsP6 that occurs in the cytosol. HPLC analysis indicates that Ins(1,4,5)P3 is converted into InsP6 via sequential phosphorylation at the 3-, 6- and 2-positions. Ins[32P]P6, isolated from cells briefly labelled with [32P]Pi, was analysed using Paramecium phytase, which removes the phosphates of InsP6 in a specific sequence. The 6-position contained significantly more 32P radioactivity than the 4- or 5-positions, indicating that the 6-position is phosphorylated after the other two positions. The results from these in vivo and in vitro experiments demonstrate a metabolic route involving the phosphorylation of Ins(1,4,5)P3 via Ins(1,3,4,5)P4 and Ins(1,3,4,5,6)P5 to InsP6 in a nucleus-associated fraction of Dictyostelium cells. PMID:8554538

  2. 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

  3. 3.6 and 4.5 μm Phase Curves and Evidence for Non-equilibrium Chemistry in the Atmosphere of Extrasolar Planet HD 189733b

    NASA Astrophysics Data System (ADS)

    Knutson, Heather A.; Lewis, Nikole; Fortney, Jonathan J.; Burrows, Adam; Showman, Adam P.; Cowan, Nicolas B.; Agol, Eric; Aigrain, Suzanne; Charbonneau, David; Deming, Drake; Désert, Jean-Michel; Henry, Gregory W.; Langton, Jonathan; Laughlin, Gregory

    2012-07-01

    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 μm bands using the Spitzer Space Telescope. When combined with previous phase curve observations at 8.0 and 24 μm, 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 μm band and 0.0982% ± 0.0089% in the 4.5 μm 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 μm, and we present new evidence indicating that the flux minimum observed in the 8 μm is likely caused by an overshooting effect in the 8 μm array. We obtain improved estimates for HD 189733b's dayside planet-star flux ratio of 0.1466% ± 0.0040% in the 3.6 μm band and 0.1787% ± 0.0038% in the 4.5 μm 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 Burrows et al. and conclude that fits to

  4. A Qualitative Comparison of the Reactivities of 3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine and 4,5-Dichloro-1,2,3-dithiazolium Chloride.

    PubMed

    Kalogirou, Andreas S; Koutentis, Panayiotis A

    2015-01-01

    The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)malononitrile. Furthermore, cyclocondensation of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with 2-aminophenol and 1,2-benzenediamines gave fused 4H-1,2,6-thiadiazines in 68%-85% yields. PMID:26274946

  5. Development of a winter wheat model in the Community Land Model (version 4.5)

    DOE PAGES

    Lu, Yaqiong; Williams, Ian N.; Bagley, Justin E.; Torn, Margaret S.; Kueppers, Lara M.

    2016-10-12

    Winter wheat is a staple crop for global food security, and is the dominant vegetation cover for a significant fraction of earth's croplands. As such, it plays an important role in carbon cycling and land-atmosphere interactions in these key regions. Accurate simulation of winter wheat growth is not only crucial for future yield prediction under changing climate, but also for understanding the energy and water cycles for winter wheat dominated regions. We developed a new winter wheat model in the Community Land Model (CLM) to better simulate wheat growth and grain production. These included schemes to represent vernalization, as wellmore » as frost tolerance and damage. We calibrated three key parameters (minimum planting temperature, maximum crop growth days, and initial value of leaf carbon allocation coefficient) and modified the grain carbon allocation algorithm for simulations at the U.S. Southern Great Plains ARM site (US-ARM), and validated the model performance at three additional sites across the continental US. We found that the new winter wheat model improved the prediction of monthly variation in leaf area index, latent heat flux, and net ecosystem exchange during the spring growing season. The model accurately simulated the interannual variation in yield at the US-ARM site, but underestimated yield at sites and in regions (Northwestern and Southeastern US) with historically greater yields.« less

  6. 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.

  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. 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.

  9. Inactivated Salmonella enterica serovar Typhimurium monophasic variant (S. Typhimurium 1,4,[5],12:i-) in sows is effective to control infection in piglets under field condition.

    PubMed

    Ruggeri, J; Pesciaroli, M; Foresti, F; Giacomini, E; Lazzaro, M; Ossiprandi, M C; Corradi, A; Lombardi, G; Pasquali, P; Alborali, G L

    2015-10-22

    The monophasic variant of Salmonella enterica serovar Typhimurium, namely Salmonella 1,4,[5],12:i-, has been increasingly responsible for foodborne human cases of disease and is most frequently detected in pork, since the variant is widely spread in pig farms. The aim of this study was to assess the efficacy of an autologous vaccine in decreasing the prevalence of Salmonella 1,4,[5],12:i-, in pigs. The trial was performed in a multisite pig production system of Northern Italy. The autogenous vaccine was prepared from the Salmonella 1,4,[5],12:i- strain isolated from the clinical case occurring in the Farm. Different immunization protocols were applied, ranging from interventions only in sows or piglets, or both. Microbiological analysis was performed to assess faecal shedding in sows and their offspring from birth till end of the production cycle and organ colonization of slaughtered pigs. Body weight of pigs was recorded at different time-points. Humoral immune response was evaluated in serum samples of sows and piglets. S. Typhimurium 1,4,[5],12:i- determines reduction of animal growth and farm production, furthermore, contamination of carcasses at the slaughterhouse. The load of bacteria entering into the food processing chain is differently influenced by the regimen of administration of inactivated vaccine. In particular, a combined vaccination of sows and their offspring was able to improve the weight gain of growing pigs, to limit Salmonella colonization of organs and to reduce the number of carrier pigs, and hence lowering the risk of introducing Salmonella organisms in the slaughter process. PMID:26260858

  10. 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

  11. 3,4,5-tricaffeoylquinic acid attenuates proteasome inhibition-mediated programmed cell death in differentiated PC12 cells.

    PubMed

    Nam, Yoon Jeong; Lee, Da Hee; Kim, Yun Jeong; Shin, Yong Kyoo; Sohn, Dong Suep; Lee, Min Sung; Lee, Chung Soo

    2014-08-01

    The dysfunction of the proteasome system is suggested to be implicated in neuronal degeneration. Caffeoylquinic acid derivatives have demonstrated anti-oxidant and anti-inflammatory effects. However, the effect of 3,4,5-tricaffeoylquinic acid on the neuronal cell death induced by proteasome inhibition has not been studied. Therefore, in the respect of cell death process, we assessed the effect of 3,4,5-tricaffeoylquinic acid on the proteasome inhibition-induced programmed cell death using differentiated PC12 cells. The proteasome inhibitors MG132 and MG115 induced a decrease in Bid, Bcl-2, and survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), and an increase in the tumor suppressor p53 levels. Treatment with 3,4,5-tricaffeoylquinic acid attenuated the proteasome inhibitor-induced changes in the programmed cell death-related protein levels, formation of reactive oxygen species, GSH depletion and cell death. The results show that 3,4,5-tricaffeoylquinic acid may attenuate the proteasome inhibitor-induced programmed cell death in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of 3,4,5-tricaffeoylquinic acid appears to be attributed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

  12. 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

  13. Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis.

    PubMed

    Wei, Ho-Chun; Rollins, Janet; Fabian, Lacramioara; Hayes, Madeline; Polevoy, Gordon; Bazinet, Christopher; Brill, Julie A

    2008-04-01

    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 gamma-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

  14. Studies of Adsorption Characteristics of Activated Carbons in between 4.5 to 10 K for Cryopump Applications

    NASA Astrophysics Data System (ADS)

    Krishnamoorthy, V.; Swarup Udgata, Satya; Shankar Tripathi, Vijai; Gangradey, Ranjana; Kasthurirengan, Srinivasan; Behera, Upendra

    2012-11-01

    Cryosorption pump is the only solution to pump helium, hydrogen and its isotopes in fusion devices. To design such pumps, knowledge of adsorption characteristics of activated carbons in the temperature range from 4.5 to 77 K is needed, but is very scarce in the open literature. Hence an experimental setup is designed and developed to measure adsorption characteristics of activated carbons down to 4.5 K. For this purpose, a commercial micropore analyzer operating down to 77K is coupled to a two-stage GM cryocooler, to enable cooling the sample temperature down to 4.5 K. A heat switch is mounted in between the second stage cold head and the sample chamber helps to vary the sample temperature from 4.5 K to 77K without affecting the performance of the cryocooler. The details of the experimental setup is presented elsewhere. We present here the experimental results of adsorption of different types of activated carbons in the temperature range 4.5K to 10 K using Helium gas as adsorbate. These results are evaluated in terms of surface area, pore sizes and their distributions. Also the effect of epoxy based adhesive used in bonding the activated carbons to the panels is evaluated. These results will be useful towards the selection of the right activated carbons for the development of cryosorption pumps.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Discovery of a Probable 4-5 Jupiter-mass Exoplanet to HD 95086 by Direct Imaging

    NASA Astrophysics Data System (ADS)

    Rameau, J.; Chauvin, G.; Lagrange, A.-M.; Boccaletti, A.; Quanz, S. P.; Bonnefoy, M.; Girard, J. H.; Delorme, P.; Desidera, S.; Klahr, H.; Mordasini, C.; Dumas, C.; 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 μm) images. This discovery is based on observations with more than a year time lapse. Our first epoch clearly revealed the source at ~= 10σ, while our second epoch lacks good observing conditions, yielding a ~= 3σ 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 3σ confidence level. The planetary nature of the source is reinforced by a non-detection in the Ks-band (2.18 μm) 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 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. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, under program Nos. 087.C-0292, 088.C.0085, 090.C-0538, 090.C-0698, and 090.C-0728.

  1. Phosphatidic acid increases inositol-1,4,5,-trisphosphate and [Ca2+]i levels in neonatal rat cardiomyocytes.

    PubMed

    Liu, P; Xu, Y; Hopfner, R L; Gopalakrishnan, V

    1999-08-25

    Phosphatidic acid (PA), which can be synthesized de novo, or as a product of phosphatidylcholine hydrolysis and/or phosphorylation of 1,2-diacylglycerol (DAG), mediates diverse cellular functions in various cell types, including cardiomyocytes. We set out to characterize the effect of PA on intracellular free calcium ([Ca2+]i) and inositol-1,4,5-trisphosphate (IP(3)) levels in primary cultures of neonatal rat cardiomyocytes. Addition of PA led to rapid, concentration and time dependent increases in both IP(3) and [Ca2+]i levels in adherent cells. There was strong correlation in the concentration-response relationships between IP(3) and [Ca2+]i increases evoked by PA. Incubation with the sarcoplasmic reticulum (SR) Ca2+ pump inhibitor, cyclopiazonic acid (CPA), significantly attenuated the PA evoked [Ca2+]i increase but had no significant effect on IP(3) accumulation. The phospholipase C (PLC) inhibitor, D-609, attenuated both IP(3) and [Ca2+]i elevations evoked by PA whereas staurosporine (STS), a potent and non-selective PKC inhibitor, had no significant effect on either. Another PLC inhibitor, U73122, but not its inactive analog, U73343, also inhibited PA evoked increases in [Ca2+]i. Depletion of extracellular calcium attenuated both basal and PA evoked increases in [Ca2+]i. The PLA(2) inhibitors, bromophenylacyl-bromide (BPB) and CDP-choline, had no effect on PA evoked [Ca2+]i responses. Neither the DAG analog, dioctanoylglycerol, nor the DAG kinase inhibitor, R59949, affected PA evoked changes in [Ca2+]i. Taken together, these data indicate that PA, in a manner independent of PKC, DAG, or PLA(2), may enhance Ca2+ release from IP(3) sensitive SR Ca(2+) stores via activation of PLC in neonatal rat cardiomyocytes.

  2. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... favor of HCEs. Example 3. Plan C is a defined benefit plan that contains an ancillary life insurance benefit available to all employees. The plan is amended to eliminate this benefit at a time when life insurance payments have been made only to beneficiaries of HCEs. Because all employees received the...

  3. The experimental and calculational thermochemistry of 1,2,4,5-benzenetetracarboxylic dianhydride: is this 10 pi multiring species aromatic?

    PubMed

    Matos, M Agostinha R; Miranda, Margarida S; Pereira, Susana M M; Morais, Victor M F; Liebman, Joel F

    2007-08-01

    The standard (p degrees = 0.1 MPa) molar enthalpy of formation of 1,2,4,5-benzenetetracarboxylic dianhydride in the gaseous phase, -826.8 +/- 3.1 kJ mol-1, was derived from the standard molar enthalpy of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry and the standard molar enthalpy of sublimation, at T = 298.15 K, measured by Calvet microcalorimetry. In addition, density functional theory calculations have been performed with the B3LYP, MPW1B95, and B3PW91 density functionals and the cc-pVTZ basis set for 1,2,4,5-benzenetetracarboxylic dianhydride and 1,2,4,5-benzenetetracarboxylic diimide. Nucleus-independent chemical shifts calculations show that the aromaticity is restricted to the benzenic ring in both compounds even though they are formally 10 pi polynuclear species. PMID:17625808

  4. 4,5-Dihydro-1,2,3-oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations.

    PubMed

    Banert, Klaus; Singh, Neeraj; Fiedler, Benjamin; Friedrich, Joachim; Korb, Marcus; Lang, Heinrich

    2015-10-19

    4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N-nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5-dihydro-1,2,3-oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by (1) H, (13) C, and (15) N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N-nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5-dihydro-1,2,3-oxadiazole. PMID:26260871

  5. 4,5-Dihydro-1,2,3-oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations.

    PubMed

    Banert, Klaus; Singh, Neeraj; Fiedler, Benjamin; Friedrich, Joachim; Korb, Marcus; Lang, Heinrich

    2015-10-19

    4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N-nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5-dihydro-1,2,3-oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by (1) H, (13) C, and (15) N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N-nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5-dihydro-1,2,3-oxadiazole.

  6. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis.

    PubMed

    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

    2014-03-01

    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.

  7. Depletion of PtdIns(4,5)P2 underlies retinal degeneration in Drosophila trp mutants

    PubMed Central

    Sengupta, Sukanya; Barber, Thomas R.; Xia, Hongai; Ready, Donald F.; Hardie, Roger C.

    2013-01-01

    Summary The prototypical transient receptor potential (TRP) channel is the major light-sensitive, and Ca2+-permeable channel in the microvillar photoreceptors of Drosophila. TRP channels are activated following hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] by the key effector enzyme phospholipase C (PLC). Mutants lacking TRP channels undergo light-dependent retinal degeneration, as a consequence of the reduced Ca2+ influx. It has been proposed that degeneration is caused by defects in the Ca2+-dependent visual pigment cycle, which result in accumulation of toxic phosphorylated metarhodopsin–arrestin complexes (MPP–Arr2). Here we show that two interventions, which prevent accumulation of MPP–Arr2, namely rearing under red light or eliminating the C-terminal rhodopsin phosphorylation sites, failed to rescue degeneration in trp mutants. Instead, degeneration in trp mutants reared under red light was rescued by mutation of PLC. Degeneration correlated closely with the light-induced depletion of PtdIns(4,5)P2 that occurs in trp mutants due to failure of Ca2+-dependent inhibition of PLC. Severe retinal degeneration was also induced in the dark in otherwise wild-type flies by overexpression of a bacterial PtdInsPn phosphatase (SigD) to deplete PtdIns(4,5)P2. In degenerating trp photoreceptors, phosphorylated Moesin, a PtdIns(4,5)P2-regulated membrane–cytoskeleton linker essential for normal microvillar morphology, was found to delocalize from the rhabdomere and there was extensive microvillar actin depolymerisation. The results suggest that compromised light-induced Ca2+ influx, due to loss of TRP channels, leads to PtdIns(4,5)P2 depletion, resulting in dephosphorylation of Moesin, actin depolymerisation and disintegration of photoreceptor structure. PMID:23378018

  8. 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.

  9. 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

  10. Process for manufacturing bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene

    DOEpatents

    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.

  11. 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.

  12. 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.

  13. 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

  14. Does Unemployment Lead to Greater Alcohol Consumption?

    PubMed

    Popovici, Ioana; French, Michael T

    2013-04-01

    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.

  15. 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.

  16. 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.

  17. Inositol 1,4,5-trisphosphate and diacylglycerol mimic bradykinin effects on mouse neuroblastoma x rat glioma hybrid cells.

    PubMed Central

    Brown, D A; Higashida, H

    1988-01-01

    1. The role of inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG) as possible mediators of the membrane current responses of NG108-15 neuroblastoma x glioma hybrid cells to bradykinin (BK, Brown & Higashida, 1988b) has been tested using intracellular ionophoresis of InsP3 and external application of phorbol dibutyrate (PDBu) and 1-oleoyl-2-acetylglycerol (OAG). 2. Intracellular ionophoresis of InsP3 into cells clamped at -30 to -50 mV produced (i) a transient outward current, (ii) a transient outward current followed by an inward current, or (iii) an inward current. All currents were accompanied by an increased input conductance. 3. The transient outward current reversed at between -80 and -90 mV. The reversal potential was shifted to more positive potentials on raising extracellular [K+], suggesting that it resulted from an increased K+ conductance. 4. The outward current was inhibited by apamin (0.4 microM) or d-tubocurarine (0.2-0.5 mM); these drugs also inhibit the outward current produced by BK or by intracellular Ca2+ injections (Brown & Higashida, 1988 a, b). The outward current was also slowly reduced in 0 mM [Ca2+] or 0.5 mM [Cd2+] plus 2 mM [Co2+] solution. 5. Ionophoretic injection of inositol 1,3,4-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, guanosine trisphosphate or inorganic phosphate did not evoke an outward current but produced only an inward current with an increased conductance, reversing at between -10 and -20 mV. 6. Bath application of PDBu (10 nM-1 microM) or OAG (1-10 microM) produced an inward current with a fall in input conductance. The inward current was voltage dependent and was accompanied by an inhibition of the time-dependent current relaxations associated with activation or deactivation of the voltage-dependent K+ current, IM. 7. PDBu did not clearly reduce the Ca2+ current or the Ca2+-dependent K+ current recorded in these cells. During superfusion with PDBu, the outward current produced by intracellular

  18. Effects of mescaline and its derivative N-[3,4,5-trimethoxyphenylethyl]-aziridine on the spatial orientation of rats in a T-maze.

    PubMed

    Koupilová, M; Herink, J

    1989-01-01

    The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.

  19. Hypervalent iodine(iii)-promoted N-incorporation into N-aryl vinylogous carbamates to quinoxaline diesters: access to 1,4,5,8-tetraazaphenanthrene.

    PubMed

    Sagar, A; Vidaycharan, Shinde; Shinde, Anand H; Sharada, Duddu S

    2016-04-26

    A novel oxidative N-incorporation strategy for synthesis of quinoxaline diesters under metal-free conditions is described for the first time. The mild reaction conditions allow for this transformation via the formation of two C(sp(2))-N bonds utilizing cheaply available NaN3 as the N-atom source. N-Aryl vinylogous carbamates in this study undergo azidation at enamino C(sp(2))-H selectively. The robustness of this strategy is further demonstrated by the synthesis of a valuable 1,4,5,8-tetraazaphenanthrene derivative using a mild and convenient approach.

  20. 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.

  1. 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.

  2. Assessing the geologic evolution of Greater Thaumasia, Mars

    NASA Astrophysics Data System (ADS)

    Hood, Don R.; Judice, Taylor; Karunatillake, Suniti; Rogers, Deanne; Dohm, James M.; Susko, David; Carnes, Lorraine K.

    2016-09-01

    The Greater Thaumasia region consists of three chemical provinces that include Syria, Solis, and Thaumasia Planae, the Corprates Rise, part of the Thaumasia Highlands, and the transition zone northwest of the Argyre basin. Chemical signatures obtained from the Mars Odyssey Gamma Ray Spectrometer suggest low abundances of K and Th to the west, with low H abundances and high Si abundances to the east, relative to the bulk Martian crust at midlatitudes. These observations are confirmed and quantified with a modified box and whisker analysis that simultaneously captures the degree of deviation and significance of the regionally anomalous chemistry. Motivated by regionally unique chemistry, as well as its diverse geological history, we characterize Greater Thaumasia in terms of chemistry, mineralogy, and mapped geology to determine how such complementary data record the evolution of this region. Our observations are inconsistent with a proposed salt-lubricated landslide origin, particularly given the lack of chemical or mineralogical signatures to support near-surface salt deposits that should arise over geological timescales. Our observations instead support magmatic processes, such as mantle evolution over geological time, which may impart the Si-enriched signature of the eastern portion of Greater Thaumasia as well as the K and Th depletion of the southeastern flank of Syria Planum. While the observed trend of decreasing K and Th from Noachian to Hesperian lavas is inconsistent with previous models of Martian mantle evolution, we see an increase in Ca content at the Noachian-Hesperian boundary, consistent with predictions from thermodynamic modeling.

  3. The 1.0-4.5 GHz Zebras in the June 6, 2000 Flare

    NASA Astrophysics Data System (ADS)

    Sawant, H. S.; Karlický, M.; Fernandes, F. C. R.; Cecatto, J. R.

    2002-01-01

    For the first time we are reporting harmonically related zebra structures above 1000 MHz, having ratio of 1:2. Zebra structures show up to 8 zebra lines. In individual zebra patterns the frequency ratio of the neighbouring zebra lines are less than 1.03 and these ratios decrease with the frequency decrease. The zebra patterns are analyzed and interpreted assuming double plasma resonance instability as the cause for their generation. The longitudinal upper hybrid waves are excited at positions of cyclotron resonances and then transformed into electromagnetic ones. Using this model the magnetic field strengths in the flaring loops are estimated in the range of 110-230 G.

  4. One-dimensional vibrational excitons in 1,2,4,5-tetrachlorobenzene

    NASA Astrophysics Data System (ADS)

    Abramson, E. H.; Jongenelis, A. P. J. M.; Schmidt, J.

    1987-10-01

    We have studied the line shapes of vibronic transitions in the phosphorescence spectrum of the one-dimensional triplet exciton of TCB between 4.2 and 0.4 K. It is shown that also the vibrational excitons are highly one dimensional. This finding is confirmed by time-resolved emission spectra. Observed vibron bandwidths vary up to 15 cm-1 with k=0 either at the top or at the bottom of the band. In contrast to the fundamental vibrations, no overtones or combination bands give evidence of a well-defined one-dimensional quasimomentum.

  5. 4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance.

    PubMed

    Urashima, Tadasu; Inamori, Hiroaki; Fukuda, Kenji; Saito, Tadao; Messer, Michael; Oftedal, Olav T

    2015-06-01

    Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg-laying followed by secretion of milk onto skin and hair in a mammary patch, in the absence of nipples. Offspring are highly immature at hatching and depend on oligosaccharide-rich milk for many months. The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(β1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized in platypus milk. In this study, acidic oligosaccharides purified from the carbohydrate fraction of platypus milk were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. All identified structures, except Neu5Ac(α2-3)Gal(β1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the pentasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-fucopentaose III). At least seven different octa- to deca-oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk contains a diverse (≥ 20) array of neutral and acidic oligosaccharides based primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and shares with echidna milk the unique feature that all identified acidic oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic milk oligosaccharides secreted onto integumental surfaces from bacterial hydrolysis via steric interference with bacterial sialidases. This may be of evolutionary significance since taxa ancestral to monotremes and other mammals are

  6. 4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance.

    PubMed

    Urashima, Tadasu; Inamori, Hiroaki; Fukuda, Kenji; Saito, Tadao; Messer, Michael; Oftedal, Olav T

    2015-06-01

    Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg-laying followed by secretion of milk onto skin and hair in a mammary patch, in the absence of nipples. Offspring are highly immature at hatching and depend on oligosaccharide-rich milk for many months. The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(β1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized in platypus milk. In this study, acidic oligosaccharides purified from the carbohydrate fraction of platypus milk were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. All identified structures, except Neu5Ac(α2-3)Gal(β1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the pentasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-fucopentaose III). At least seven different octa- to deca-oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk contains a diverse (≥ 20) array of neutral and acidic oligosaccharides based primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and shares with echidna milk the unique feature that all identified acidic oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic milk oligosaccharides secreted onto integumental surfaces from bacterial hydrolysis via steric interference with bacterial sialidases. This may be of evolutionary significance since taxa ancestral to monotremes and other mammals are

  7. Climate-vegetation interactions in the coupled RegCM4 - CLM4.5 CNDV model

    NASA Astrophysics Data System (ADS)

    Caporaso, Luca; Giuliani, Graziano; Giorgi, Filippo

    2016-04-01

    We use the latest version of International Center for Theoretical Physics (ICTP) regional climate model (RegCM4) coupled with the Community Land Model version 4.5 (CLM4.5) including a dynamic vegetation model to study biogeophysical feedbacks in the climate system related to vegetation composition and structure. Sets of parallel experiments are conducted over the Africa and South America CORDEX domains using the RegCM4-CLM4.5 in its standard configuration and with the CNDV activated (CLM 4.5 with both the Carbon Nitrogen and the Dynamic Vegetation Model activated). The potential role of regional vegetation feedbacks within the climate system and the impact of climate variability and change on the ecosystem dynamics is assessed for both domains. In addition, the sensitivity to initial vegetation conditions and different idealized climate forcings is investigated. Preliminary results show that the changes in the climate forcing can have substantial effects on the dynamics and evolution of different vegetation types over both domains, and that the vegetation coupling can have a substantial effect on the simulated regional climate regimes. Our results thus indicate on the one hand that climate change can have profound effects on the evolution of important ecosystems for the two regions, and on the other that vegetation dynamics can indeed affect the climate response at the regional scale.

  8. Efficient metal-free synthesis of various pyrido[2',1':2,3]imidazo- [4,5-b]quinolines.

    PubMed

    Arnould, Mathieu; Hiebel, Marie-Aude; Massip, Stéphane; Léger, Jean Michel; Jarry, Christian; Berteina-Raboin, Sabine; Guillaumet, Gérald

    2013-09-01

    Dancing with diversity: The synthesis of diverse pyrido[2',1':2,3]imidazo[4,5-b]quinolines bearing several substitution patterns was developed based on combining a multicomponent reaction (Groebke-Blackburn-Bienaymé reaction) with an original cyclization as a secondary transformation (see scheme; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene).

  9. Motion Popout in Selective Visual Orienting at 4.5 but Not at 2 Months in Human Infants

    ERIC Educational Resources Information Center

    Dannemiller, James L.

    2005-01-01

    The effect of element density on selective orienting was examined in 2 experiments with 2- and 4.5-month-old infants. Selective visual orienting to a singleton oscillating target that appeared with other static bars was used to study the effects of element density. Increasing the set size and density of the static bars decreased selective…

  10. PtdIns(3,4,5)P(3) and inositol depletion as a cellular target of mood stabilizers.

    PubMed

    Teo, Regina; King, Jason; Dalton, Emma; Ryves, Jonathan; Williams, Robin S B; Harwood, Adrian J

    2009-10-01

    Lithium (Li(+)) is the mood stabilizer most frequently used in the treatment of bipolar mood disorder; however, its therapeutic mechanism is unknown. In the 1980s, Berridge and colleagues proposed that Li(+) treatment acts via inhibition of IMPase (inositol monophosphatase) to deplete the cellular concentration of myo-inositol. Inositol depletion is also seen with the alternative mood stabilizers VPA (valproic acid) and CBZ (carbamazepine), suggesting a common therapeutic action. All three drugs cause changes in neuronal cell morphology and cell chemotaxis; however, it is unclear how reduced cellular inositol modulates these changes in cell behaviour. It is often assumed that reduced inositol suppresses Ins(1,4,5)P(3), a major intracellular signal molecule, but there are other important phosphoinostide-based signal molecules in the cell. In the present paper, we discuss evidence that Li(+) has a substantial effect on PtdIns(3,4,5)P(3), an important signal molecule within the nervous system. As seen for Ins(1,4,5)P(3) signalling, suppression of PtdIns(3,4,5)P(3) signalling also occurs via an inositol-depletion mechanism. This has implications for the cellular mechanisms controlling phosphoinositide signalling, and offers insight into the genetics underlying risk of bipolar mood disorder.

  11. Synthesis of methylamino-2-phenyl-2-butyl-3,4,5-trimethoxybenzoate, the main bioactive metabolite of trimebutine maleate.

    PubMed

    Martin, A; Figadère, B; Saivin, S; Houin, G; Chomard, J M; Cahiez, G

    2000-06-01

    The first synthesis of the methylamino-2-phenyl-2-butyl-3,4,5-trimethoxybenzoate (desmethyltrimebutine) I is described. This compound is the main bioactive metabolite of trimebutine II (Debridat, CAS 39133-31-8), an antispasmodic widely used for intestinal diseases since 1969. It was used for pharmacokinetic and bioequivalence studies. PMID:10918948

  12. Inositol 1,4,5-trisphosphate 3-kinase B controls survival and prevents anergy in B cells.

    PubMed

    Maréchal, Yoann; Quéant, Séverine; Polizzi, Selena; Pouillon, Valérie; Schurmans, Stéphane

    2011-01-01

    Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), its reaction product, play an important role in the control of B lymphocyte fate and function in vivo. In order to investigate the fine mechanisms of Itpkb and Ins(1,3,4,5)P4 action in B cells, we crossed Itpkb(-/-) mice with transgenic mice expressing a 3-83μδ B cell receptor (BCR) specific for membrane-bound MHC-I H2-K(b) and H2-K(k) molecules. On a non-deleting H2-K(d) genetic background, we show that Itpkb is important for the control of Bim protein expression and B cell survival rather than for the control of B cell development from one stage to another. Analyses of cell surface markers expression, proapoptotic Bim protein expression, in vitro survival and in vivo turnover demonstrated that BCR transgenic Itpkb(-/-) B cells exhibit an anergic phenotype with the notable exception of their enhanced antigen-induced calcium signalling. On a deleting H2-K(b) genetic background, we show that Itpkb is not essential for BCR editing or negative selection. These data establish Itpkb as an important regulator of B cell survival and anergy in vivo.

  13. Netscape Communicator 4.5. Volume II: Beyond the Basics. Advanced Searches, Multimedia, and Composing a Web Page.

    ERIC Educational Resources Information Center

    Gallo, Gail; Wichowski, Chester P.

    This second of two guides on Netscape Communicator 4.5 contains six lessons on advanced searches, multimedia, and composing a World Wide Web page. Lesson 1 is a review of the Navigator window, toolbars, and menus. Lesson 2 covers AltaVista's advanced search tips, searching for information excluding certain text, and advanced and nested Boolean…

  14. Dynamic stabilization for L4-5 spondylolisthesis: comparison with minimally invasive transforaminal lumbar interbody fusion with more than 2 years of follow-up.

    PubMed

    Kuo, Chao-Hung; Chang, Peng-Yuan; Wu, Jau-Ching; Chang, Hsuan-Kan; Fay, Li-Yu; Tu, Tsung-Hsi; Cheng, Henrich; Huang, Wen-Cheng

    2016-01-01

    OBJECTIVE In the past decade, dynamic stabilization has been an emerging option of surgical treatment for lumbar spondylosis. However, the application of this dynamic construct for mild spondylolisthesis and its clinical outcomes remain uncertain. This study aimed to compare the outcomes of Dynesys dynamic stabilization (DDS) with minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for the management of single-level spondylolisthesis at L4-5. METHODS This study retrospectively reviewed 91 consecutive patients with Meyerding Grade I spondylolisthesis at L4-5 who were managed with surgery. Patients were divided into 2 groups: DDS and MI-TLIF. The DDS group was composed of patients who underwent standard laminectomy and the DDS system. The MI-TLIF group was composed of patients who underwent MI-TLIF. Clinical outcomes were evaluated by visual analog scale for back and leg pain, Oswestry Disability Index, and Japanese Orthopaedic Association scores at each time point of evaluation. Evaluations included radiographs and CT scans for every patient for 2 years after surgery. RESULTS A total of 86 patients with L4-5 spondylolisthesis completed the follow-up of more than 2 years and were included in the analysis (follow-up rate of 94.5%). There were 64 patients in the DDS group and 22 patients in the MI-TLIF group, and the overall mean follow-up was 32.7 months. Between the 2 groups, there were no differences in demographic data (e.g., age, sex, and body mass index) or preoperative clinical evaluations (e.g., visual analog scale back and leg pain, Oswestry Disability Index, and Japanese Orthopaedic Association scores). The mean estimated blood loss of the MI-TLIF group was lower, whereas the operation time was longer compared with the DDS group (both p < 0.001). For both groups, clinical outcomes were significantly improved at 6, 12, 18, and 24 months after surgery compared with preoperative clinical status. Moreover, there were no differences between the 2

  15. Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels.

    PubMed

    Dai, Gucan; Yu, Haijie; Kruse, Martin; Traynor-Kaplan, Alexis; Hille, Bertil

    2016-06-01

    Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na(+)/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several "physiological" manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells. PMID:27217553

  16. Phosphatidylinositol 4,5-Bisphosphate Influences PIN Polarization by Controlling Clathrin-Mediated Membrane Trafficking in Arabidopsis[C][W

    PubMed Central

    Ischebeck, Till; Werner, Stephanie; Krishnamoorthy, Praveen; Lerche, Jennifer; Meijón, Mónica; Stenzel, Irene; Löfke, Christian; Wiessner, Theresa; Im, Yang Ju; Perera, Imara Y.; Iven, Tim; Feussner, Ivo; Busch, Wolfgang; Boss, Wendy F.; Teichmann, Thomas; Hause, Bettina; Persson, Staffan; Heilmann, Ingo

    2013-01-01

    The functions of the minor phospholipid phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] during vegetative plant growth remain obscure. Here, we targeted two related phosphatidylinositol 4-phosphate 5-kinases (PI4P 5-kinases) PIP5K1 and PIP5K2, which are expressed ubiquitously in Arabidopsis thaliana. A pip5k1 pip5k2 double mutant with reduced PtdIns(4,5)P2 levels showed dwarf stature and phenotypes suggesting defects in auxin distribution. The roots of the pip5k1 pip5k2 double mutant had normal auxin levels but reduced auxin transport and altered distribution. Fluorescence-tagged auxin efflux carriers PIN-FORMED (PIN1)–green fluorescent protein (GFP) and PIN2-GFP displayed abnormal, partially apolar distribution. Furthermore, fewer brefeldin A–induced endosomal bodies decorated by PIN1-GFP or PIN2-GFP formed in pip5k1 pip5k2 mutants. Inducible overexpressor lines for PIP5K1 or PIP5K2 also exhibited phenotypes indicating misregulation of auxin-dependent processes, and immunolocalization showed reduced membrane association of PIN1 and PIN2. PIN cycling and polarization require clathrin-mediated endocytosis and labeled clathrin light chain also displayed altered localization patterns in the pip5k1 pip5k2 double mutant, consistent with a role for PtdIns(4,5)P2 in the regulation of clathrin-mediated endocytosis. Further biochemical tests on subcellular fractions enriched for clathrin-coated vesicles (CCVs) indicated that pip5k1 and pip5k2 mutants have reduced CCV-associated PI4P 5-kinase activity. Together, the data indicate an important role for PtdIns(4,5)P2 in the control of clathrin dynamics and in auxin distribution in Arabidopsis. PMID:24326589

  17. Fire, Vegetation, Climate Interactions in the Greater Yellowstone Ecosystem: Tipping Points and Landscape Vulnerability

    NASA Astrophysics Data System (ADS)

    Smithwick, E. A.; Westerling, A. L.; Turner, M. G.; Romme, W. H.; Ryan, M. G.

    2010-12-01

    The subalpine forests of the Greater Yellowstone Ecosystem are vulnerable to extreme fires under climate change but the consequences of repeated large fire events on vegetation dynamics and carbon (C) storage are unknown. Shifts in post-fire succession may represent fundamental changes in the potential of western forests to sequester atmospheric C. In this study, we ask whether the projected changes in climate and fire for the region are sufficient to significantly inhibit post-fire forest recovery. We hypothesize that vegetation communities contribute differentially to future landscape C flux because of different sensitivities to future climate and fire combinations, with largest changes expected for conditions that switch forest to grassland. Here, we used an ecosystem model (CENTURY v. 4.5) to forecast C storage among dominant vegetation communities in Greater Yellowstone associated with different fire severities, regeneration rates, and climates: lodgepole pine, warm-dry and cool-moist conifers, aspen, and grassland/shrubland. The model was parameterized for each vegetation type using empirical data on post-fire C loss, recovery rates, and C storage potential. Vegetation types were run forward under future climate scenarios: downscaled (1/8 degree grid) A2 and B1 emissions pathways for four global climate models (NCAR PCM1, GFDL CM2.3, CNRM-CM3, CCSM3) for three locations in Yellowstone National Park (Old Faithful, Lake Yellowstone, and Lamar) that represent current climate and vegetation conditions in the park. Results indicated that under historical climate and contemporary fire return intervals (172 yrs), cumulative C emissions from fire were greatest when fire severity was low, largely due to higher fuel buildup. Reductions in C storage under future climate were greatest when fire return intervals were less than ca. 80 yrs - the time needed to replace C stocks consumed by fire, and when climate conditions were more suitable for grassland versus forest, but

  18. Federal Emergency Management Information System (FEMIS) data management guide, version 1.4.5

    SciTech Connect

    Burnett, R.A.; Downing, T.R.; Gaustad, K.L.

    1998-06-26

    The Federal Emergency Management Information System (FEMIS) information resources are described in this FEMIS Data Management Guide. To comprehend what types of data are present, where the data is located, and how it is managed during the life span of the system, a basic understanding of the FEMIS architecture is necessary. The system is being developed by Pacific Northwest National Laboratory (PNNL) and is designed for a single Chemical Stockpile Emergency Preparedness Program (CSEPP) site that has multiple Emergency Operations Centers (EOCs). The capability to connect to remote CSEPP sites and share information will be present in a future release. Each EOC has personal computers (PCs) that emergency planners and operations personnel use to do their jobs. These PCs are connected via a local area network (LAN) to servers that provide efficient EOC-wide services. Each EOC is interconnected to other EOCs via telecommunications links. FEMIS is a client/server system where much of the application software is located in the client PC. This client software integrates the FEMIS application, government furnished dispersion and evacuation models, and Commercial-Off-The-Shelf (COTS) software tools such as the ArcView geographic information system (GIS) and Microsoft Project (electron planning). A UNIX server provides data management services, ARC/INFO GIS capabilities, evacuation (Evac) modeling, electron main (E-mail), and meteorological (Met) input processing. A PC communication utility is available to interface with external subsystems. At this time, the weather collection system (Handar Met System) is the only external subsystem.

  19. Patients with Glasgow Coma Scale scores 3, 4, 5 after gunshot wounds to the brain.

    PubMed

    Kaufman, H H; Levy, M L; Stone, J L; Masri, L S; Lichtor, T; Lavine, S D; Fitzgerald, L F; Apuzzo, M L

    1995-10-01

    Even this information is only partial. To study fully the effects of treatment would require optimal care at all points from time of injury, including rapid prehospital resuscitation, rapid transport to an optimally equipped and staffed hospital, immediate evaluation and treatment of the initial injury and all complications, rapid and comprehensive rehabilitation, and supportive and flexible home and work settings for the patient on discharge. Patients would need to be stratified for premorbid characteristics, including intelligence, personal traits, and training. Prolonged follow-up, possibly for several years, would be required to determine true outcome. No current study contains sufficient numbers of patients treated optimally and studied for prolonged periods, but this should be done. One way of looking at such patients is to decide that many should be treated to salvage a few. The other way of looking at them is that so many must receive care, at great emotional and economic cost to themselves and others, that such treatment is inappropriate for any of them. Treating all such patients would be a major undertaking. If most of these patients were treated vigorously, a great proportion of them would still die but probably not for a number of days. During this period, their families would be under extreme stress. Once stabilized and receiving ongoing care, some patients would enter a permanent vegetative state and survive for prolonged periods until their prognosis was clear and care was withdrawn, again causing family stress as well as high cost. Some would likely survive although impaired. The charges and real costs of care for all these patients would be tremendous. The question therefore arises as to how to decide what to do about caring for a large group of patients whose maximal care would be costly in emotional and financial terms, particularly at a time when it is recognized that resources for medical care are going to be limited. When discussing such

  20. CH4 parameter estimation in CLM4.5bgc using surrogate global optimization

    NASA Astrophysics Data System (ADS)

    Müller, J.; Paudel, R.; Shoemaker, C. A.; Woodbury, J.; Wang, Y.; Mahowald, N.

    2015-10-01

    Over the anthropocene methane has increased dramatically. Wetlands are one of the major sources of methane to the atmosphere, but the role of changes in wetland emissions is not well understood. The Community Land Model (CLM) of the Community Earth System Models contains a module to estimate methane emissions from natural wetlands and rice paddies. Our comparison of CH4 emission observations at 16 sites around the planet reveals, however, that there are large discrepancies between the CLM predictions and the observations. The goal of our study is to adjust the model parameters in order to minimize the root mean squared error (RMSE) between model predictions and observations. These parameters have been selected based on a sensitivity analysis. Because of the cost associated with running the CLM simulation (15 to 30 min on the Yellowstone Supercomputing Facility), only relatively few simulations can be allowed in order to find a near-optimal solution within an acceptable time. Our results indicate that the parameter estimation problem has multiple local minima. Hence, we use a computationally efficient global optimization algorithm that uses a radial basis function (RBF) surrogate model to approximate the objective function. We use the information from the RBF to select parameter values that are most promising with respect to improving the objective function value. We show with pseudo data that our optimization algorithm is able to make excellent progress with respect to decreasing the RMSE. Using the true CH4 emission observations for optimizing the parameters, we are able to significantly reduce the overall RMSE between observations and model predictions by about 50 %. The methane emission predictions of the CLM using the optimized parameters agree better with the observed methane emission data in northern and tropical latitudes. With the optimized parameters, the methane emission predictions are higher in northern latitudes than when the default parameters are

  1. Addition polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and Bis-dienes. 2: Evidence for thermal dehydration occurring in the cure process

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.; Olshavsky, Michael A.; Meador, Michael A.; Ahn, Myong-Ku

    1988-01-01

    Diels-Alder cycloaddition copolymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and anthracene end-capped polyimide oligomers appear, by thermogravimetric analysis (TGA), to undergo dehydration at elevated temperatures. This would produce thermally stable pentiptycene units along the polymer backbone, and render the polymers incapable of unzipping through a retro-Diels-Alder pathway. High resolution solid 13C nuclear magnetic resonance (NMR) of one formulation of the polymer system before and after heating at elevated temperatures, shows this to indeed be the case. NMR spectra of solid samples of the polymer before and after heating correlated well with those of the parent pentiptycene model compound before and after acid-catalyzed dehydration. Isothermal gravimetric analyses and viscosities of the polymer before and after heat treatment support dehydration as a mechanism for the cure reaction.

  2. The synthesis and crystal structure of 2-[4(S)-4,5-dihydro-4-phenyl-2-oxazolinyl]-benzenamine, and 2-[4(S)-4,5-dihydro-4-benzyl-2-oxazolinyl]-benzenamine

    NASA Astrophysics Data System (ADS)

    Mei, Luo; Hai, Zhang Jia; Hao, Yin; Min, Pang Wei; Liang, Hu Ke

    2010-12-01

    Two oxazolines compound 1a and 1b, 2-[4( S)-4,5-dihydro-4-phenyl-2-ozazolinyl-benzenamine, and (C15H14N2O), 2-[4( S)-4,5-dihydro-4-benzyl-2-ozazolinyl-benzenamine (C16H16N2O) were obtained in moderate yield from the reactions of 2-aminobenzonitrile with optically active L-(+)-Phenylglycinol and L-(+)-Phenylalaninol, respectively, in chlorobenzene under dry, anaerobic conditions. ZnCl2 was dried under vacuum and acted as a Lewis acid catalyst in this reaction. The structures of 1a and 1b were determined by X-ray diffraction and NMR. There exist intra- and intermolecular N-H…N hydrogen bonds in the crystal structure.

  3. Susceptibility of caffeine- and Ins(1,4,5)P3-induced contractions to oxidants in permeabilized vascular smooth muscle.

    PubMed

    Wada, S; Okabe, E

    1997-02-01

    Two principal pathways of Ca2+ release from the sarcoplasmic reticulum of excitable and non-excitable cells have been described: one pathway dependent on the second messenger D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), and a second pathway sensitive to Ca2+ and regulated by caffeine and ryanodine. It was found that the Ca(2+)-pump activity of vascular smooth muscle sarcoplasmic reticulum is inhibited by superoxide anion radicals (O2.-); however, the effects of reactive oxygen intermediates on sarcoplasmic reticulum Ca2+ release in vascular muscle cells are not well defined. The purpose of the present study was to evaluate the effects of reactive oxygen intermediates generated from the hypoxanthine/xanthine oxidase reaction system on contractions induced by caffeine, Ins(1,4,5)P3 and norepinephrine in staphylococcal alpha-toxin-permeabilized rabbit mesenteric arteries. This system generates O2.-, H2O2, and hydroxyl radicals. We wished to identify which class of reactive oxygen intermediates is responsible for the associated loss of vascular smooth muscle contractile function. Caffeine and Ins(1,4,5)P3 produced a transient contraction when the sarcoplasmic reticulum of the permeabilized, preparations was preloaded with pCa 7.0 solution for 5 min before washing with 0.5 mM EGTA solution; norepinephrine also produced a transient contraction. Exposure of the preparations to hypoxanthine/xanthine oxidase (for 30 min) attenuated caffeine-induced contraction, but was without effect on Ins(1,4,5)P3-induced contraction. The observed effect of hypoxanthine/xanthine oxidase exposure was superoxide dismutase-inhibitable, suggesting O2.- involvement. Hypoxanthine/xanthine oxidase also inhibited norepinephrine-induced contraction. The effect of hypoxanthine/xanthine oxidase on norepinephrine contraction was protected by catalase, but not by superoxide dismutase and dimethyl sulfoxide; exogenously added H2O2 mimicked the effect of hypoxanthine/xanthine oxidase exposure. H2O

  4. Study and optimization of negative polarity rod pinch diode as flash radiography source at 4.5 MV

    NASA Astrophysics Data System (ADS)

    Etchessahar, Bertrand; Bernigaud, Virgile; Caron, Michel; Cartier, Frédéric; Cartier, Stéphanie; Hourdin, Laurent; Magnin, Laurent; Nicolas, Rémi; Poulet, Frédéric; Rosol, Rodolphe; Tailleur, Yaël; Toury, Martial; Compant La Fontaine, Antoine; Bicrel, Béatrice; Cassany, Bruno; Desanlis, Thierry; Voisin, Luc; Hébert, David; Delbos, Christophe; Garrigues, Alain; Soleilhavoup, Isabelle

    2012-09-01

    The negative polarity rod pinch diode (NPRPD) is a potential millimeter spot size radiography source for high voltage generators (4 to 8 MV) [Cooperstein et al., "Considerations of rod-pinch diode operation in negative polarity for radiography," in Proceedings of the 14th IEEE Pulsed Power Conference, 2003, pp. 975-978]. The NPRPD consists of a small diameter (few mm) cylindrical anode extending from the front end of the vacuum cell through a thin annular cathode, held by a central conductor. The polarity has been inverted when compared to the original rod pinch diode [Cooperstein et al., "Theoretical modeling and experimental characterization of a rod-pinch diode," Phys. Plasmas 8(10), 4618-4636 (2001)] in order to take advantage from the maximal x-ray emission toward the anode holder at such a voltage [Swanekamp et al., "Evaluation of self-magnetically pinched diodes up to 10 MV as high resolution flash X-ray sources," IEEE Trans. Plasma Sci. 32(5), 2004-2016 (2004). We have studied this diode at 4.5 MV, driven by the ASTERIX generator [Raboisson et al., "ASTERIX, a high intensity X-ray generator," in Proceedings of the 7th IEEE Pulsed Power Conference, 1989, pp. 567-570.]. This generator, made up of a capacitor bank and a Blumlein line, was initially designed to test the behavior of electronic devices under irradiation. In our experiments, the vacuum diode has been modified in order to set up flash a radiographic diode [Etchessahar et al., "Negative polarity rod pinch diode experiments on the ASTERIX generator," in Conference Records-Abstracts, 37th IEEE International Conference on Plasma Science, 2010]. The experiments and numerical simulations presented here allowed the observation and analysis of various physical phenomena associated with the diode operation. Also, the influence of several experimental parameters, such as cathode and anode diameters, materials and surface states, was examined. In order to achieve the most comprehensive characterization of the

  5. Study and optimization of negative polarity rod pinch diode as flash radiography source at 4.5 MV

    SciTech Connect

    Etchessahar, Bertrand; Bicrel, Beatrice; Cassany, Bruno; Desanlis, Thierry; Voisin, Luc; Hebert, David; Bernigaud, Virgile; Magnin, Laurent; Nicolas, Remi; Poulet, Frederic; Tailleur, Yaeel; Caron, Michel; Cartier, Frederic; Cartier, Stephanie; Hourdin, Laurent; Rosol, Rodolphe; Toury, Martial; Delbos, Christophe; Garrigues, Alain; Soleilhavoup, Isabelle; and others

    2012-09-15

    The negative polarity rod pinch diode (NPRPD) is a potential millimeter spot size radiography source for high voltage generators (4 to 8 MV) [Cooperstein et al., 'Considerations of rod-pinch diode operation in negative polarity for radiography,' in Proceedings of the 14th IEEE Pulsed Power Conference, 2003, pp. 975-978]. The NPRPD consists of a small diameter (few mm) cylindrical anode extending from the front end of the vacuum cell through a thin annular cathode, held by a central conductor. The polarity has been inverted when compared to the original rod pinch diode [Cooperstein et al., 'Theoretical modeling and experimental characterization of a rod-pinch diode,' Phys. Plasmas 8(10), 4618-4636 (2001)] in order to take advantage from the maximal x-ray emission toward the anode holder at such a voltage [Swanekamp et al., 'Evaluation of self-magnetically pinched diodes up to 10 MV as high resolution flash X-ray sources,' IEEE Trans. Plasma Sci. 32(5), 2004-2016 (2004). We have studied this diode at 4.5 MV, driven by the ASTERIX generator [Raboisson et al., 'ASTERIX, a high intensity X-ray generator,' in Proceedings of the 7th IEEE Pulsed Power Conference, 1989, pp. 567-570.]. This generator, made up of a capacitor bank and a Blumlein line, was initially designed to test the behavior of electronic devices under irradiation. In our experiments, the vacuum diode has been modified in order to set up flash a radiographic diode [Etchessahar et al., 'Negative polarity rod pinch diode experiments on the ASTERIX generator,' in Conference Records-Abstracts, 37th IEEE International Conference on Plasma Science, 2010]. The experiments and numerical simulations presented here allowed the observation and analysis of various physical phenomena associated with the diode operation. Also, the influence of several experimental parameters, such as cathode and anode diameters, materials and surface states, was examined. In order to achieve the most comprehensive characterization of the

  6. [The dynamics of the domains of the IP3-binding site of the inositol-1,4,5-triphosphate-sensitive calcium channel, induced by inositol-1,4,5-triphosphate and calcium].

    PubMed

    Veresov, V G; Konev, S V

    2005-01-01

    The dynamics of the inositol-1,4,5-triphosphate-sensitive calcium channel after binding of inositol-1,4,5-triphosphate and Ca2+ was analyzed by the Monte Carlo minimization technique. It was shown that the binding of Ca2+ with the unliganded receptor (channel) leads to a turning of the beta-sheet domain relative to the alpha-helical domain with the formation of the receptor conformation that is open for the entry of ions into the cytoplasmic channel vestibule, sterically closed for their passage through the vestibule in the part adjacent to the alpha-helical domains, and unfavourable for subsequent binding of inositol-1,4,5-triphosphate with the receptor. When both co-agonists bind to the receptor, the structure rearrangements induced eliminate both these steric obstacles for the passage of ions through the IP3-binding domain: one at the entrance of the channel cytoplasmic vestibule and the other that is placed deeper in the vestibule near the alpha-domains. The role of the dynamics of the receptor binding core in the IP3-sensitive channel gating is discussed.

  7. One-pot Sequential Reactions Featuring a Copper-catalyzed Amination Leading to Pyrido[2',1':2,3]imidazo[4,5-c]quinolines and Dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines.

    PubMed

    Fan, Xue-Sen; Zhang, Ju; Li, Bin; Zhang, Xin-Ying

    2015-06-01

    Tetracyclic skeletons combining an imidazo[1,2-a]pyridine moiety with a quinoline framework such as pyrido[2',1':2,3]imidazo[4,5-b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2',1':2,3]imidazo[4,5-c]quinolines through one-pot sequential reactions of commercially available or readily obtainable 2-aminopyridines, 2-bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step-by-step operations. PMID:25865134

  8. One-pot Sequential Reactions Featuring a Copper-catalyzed Amination Leading to Pyrido[2',1':2,3]imidazo[4,5-c]quinolines and Dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines.

    PubMed

    Fan, Xue-Sen; Zhang, Ju; Li, Bin; Zhang, Xin-Ying

    2015-06-01

    Tetracyclic skeletons combining an imidazo[1,2-a]pyridine moiety with a quinoline framework such as pyrido[2',1':2,3]imidazo[4,5-b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2',1':2,3]imidazo[4,5-c]quinolines through one-pot sequential reactions of commercially available or readily obtainable 2-aminopyridines, 2-bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2',1':2,3]imidazo[4,5-c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step-by-step operations.

  9. Ins(1,4,5)P{sub 3} facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    SciTech Connect

    Sun, Jing; Ogata, Shigenori; Segawa, Masaru; Usune, Sadaharu; Zhao, Yumei; Katsuragi, Takeshi

    2010-07-02

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 {mu}g) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 {mu}M inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca{sup 2+}-removal from ICM and by adding thapsigargin, a Ca{sup 2+}-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P{sub 3} receptor antagonists. Administration of 500 {mu}M adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P{sub 3}.

  10. The nitration pattern of energetic 3,6-diamino-1,2,4,5-tetrazine derivatives containing azole functional groups.

    PubMed

    Aizikovich, A; Shlomovich, A; Cohen, A; Gozin, M

    2015-08-21

    One of the successful strategies for the design of promising new energetic materials is the incorporation of both fuel and oxidizer moieties into the same molecule. Therefore, during recent years, synthesis of various nitro-azole derivatives, as compounds with a more balanced oxygen content, has become very popular. In the framework of this effort, we studied nitration of N(3),N(6)-bis(1H-tetrazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine (BTATz; ) and its alkylated derivative N(3),N(6)-bis(2-methyl-2H-tetrazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine , using a (15)N-labeled nitration agent and monitoring and analyzing products of these reactions by (15)N NMR. It was seen that the nitration of both compounds takes place only on the exocyclic ("bridging") secondary amine groups. Possible tetranitro derivative isomers N,N'-(1,2,4,5-tetrazine-3,6-diyl)bis(N-(1-nitro-1H-tetrazol-5-yl)-nitramide) and N,N'-(1,2,4,5-tetrazine-3,6-diyl)bis(N-(2-nitro-2H-tetrazol-5-yl)nitramide) , both of which have OB = 0% and calculated VODs of 9790 and 9903 m s(-1), respectively, could not be observed in the reaction mixtures, during the in situ(15)N NMR monitoring of nitration of , using (15)N-labeled nitrating agents. Following a similar strategy, a new analog of BTATz - N(3),N(6)-Bis(1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine was obtained and its nitration was studied. The reaction of with a HNO3-Ac2O nitration mixture resulted in the formation of a new N(3),N(6)-bis(3-nitro-1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine derivative in a moderate yield. Structures and properties of (in the form of its perchlorate salt, ) and were measured by FTIR, multinuclear NMR, MS, DSC and X-ray crystallography. It is important to note that compound exhibits exothermic decomposition at 302 °C (DSC) and >353 N (sensitivity to friction), making it a highly-promising thermally-insensitive energetic material for further development.

  11. Characterization of an Arabidopsis inositol 1,3,4,5,6-pentakisphosphate 2-kinase (AtIPK1)

    PubMed Central

    Sweetman, Dylan; Johnson, Sue; Caddick, Samuel E. K.; Hanke, David E.; Brearley, Charles A.

    2005-01-01

    The metabolic pathway(s) by which plants synthesize InsP6 (inositol 1,2,3,4,5,6-hexakisphosphate) remains largely undefined [Shears (1998) Biochim. Biophys. Acta 1436, 49–67], while the identities of the genes that encode enzymes catalysing individual steps in these pathways are, with the notable exception of myo-inositol phosphate synthase and ZmIpk [Shi, Wang, Wu, Hazebroek, Meeley and Ertl (2003) Plant Physiol. 131, 507–515], unidentified. A yeast enzyme, ScIPK1, catalyses the synthesis of InsP6 by 2-phosphorylation of Ins(1,3,4,5,6)P5 (inositol 1,3,4,5,6-pentakisphosphate). A human orthologue, HsIPK1, is able to substitute for yeast ScIPK1, restoring InsP6 production in a Saccharomyces cerevisiae mutant strain lacking the ScIPK1 open reading frame (ScIpk1Δ). We have identified an Arabidopsis genomic sequence, AtIPK1, encoding an Ins(1,3,4,5,6)P5 2-kinase. Inclusion of the AtIPK1 protein in alignments of amino acid sequences reveals that human and Arabidopis kinases are more similar to each other than to the S. cerevisiae enzyme, and further identifies an additional motif. Recombinant AtIPK1 protein expressed in Escherichia coli catalysed the synthesis of InsP6 from Ins(1,3,4,5,6)P5. The enzyme obeyed Michaelis–Menten kinetics with an apparent Vmax of 35 nmol·min−1·(mg of protein)−1 and a Km for Ins(1,3,4,5,6)P5 of 22 μM at 0.4 mM ATP. RT (reverse transcriptase)–PCR analysis of AtIPK1 transcripts revealed that AtIPK1 is expressed in siliques, leaves and cauline leaves. In situ hybridization experiments further revealed strong expression of AtIPK1 in male and female organs of flower buds. Expression of AtIPK1 protein in an ScIpk1Δ mutant strain restored InsP6 production and rescued the temperature-sensitive growth phenotype of the yeast. PMID:16223361

  12. Phosphatidylinositol-(4,5)-Bisphosphate Acyl Chains Differentiate Membrane Binding of HIV-1 Gag from That of the Phospholipase Cδ1 Pleckstrin Homology Domain

    PubMed Central

    Olety, Balaji; Veatch, Sarah L.

    2015-01-01

    ABSTRACT HIV-1 Gag, which drives virion assembly, interacts with a plasma membrane (PM)-specific phosphoinositide, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. While cellular acidic phospholipid-binding proteins/domains, such as the PI(4,5)P2-specific pleckstrin homology domain of phospholipase Cδ1 (PHPLCδ1), mediate headgroup-specific interactions with corresponding phospholipids, the exact nature of the Gag-PI(4,5)P2 interaction remains undetermined. In this study, we used giant unilamellar vesicles (GUVs) to examine how PI(4,5)P2 with unsaturated or saturated acyl chains affect membrane binding of PHPLCδ1 and Gag. Both unsaturated dioleoyl-PI(4,5)P2 [DO-PI(4,5)P2] and saturated dipalmitoyl-PI(4,5)P2 [DP-PI(4,5)P2] successfully recruited PHPLCδ1 to membranes of single-phase GUVs. In contrast, DO-PI(4,5)P2 but not DP-PI(4,5)P2 recruited Gag to GUVs, indicating that PI(4,5)P2 acyl chains contribute to stable membrane binding of Gag. GUVs containing PI(4,5)P2, cholesterol, and dipalmitoyl phosphatidylserine separated into two coexisting phases: one was a liquid phase, and the other appeared to be a phosphatidylserine-enriched gel phase. In these vesicles, the liquid phase recruited PHPLCδ1 regardless of PI(4,5)P2 acyl chains. Likewise, Gag bound to the liquid phase when PI(4,5)P2 had DO-acyl chains. DP-PI(4,5)P2-containing GUVs showed no detectable Gag binding to the liquid phase. Unexpectedly, however, DP-PI(4,5)P2 still promoted recruitment of Gag, but not PHPLCδ1, to the dipalmitoyl-phosphatidylserine-enriched gel phase of these GUVs. Altogether, these results revealed different roles for PI(4,5)P2 acyl chains in membrane binding of two PI(4,5)P2-binding proteins, Gag and PHPLCδ1. Notably, we observed that nonmyristylated Gag retains the preference for PI(4,5)P2 containing an unsaturated acyl chain over DP-PI(4,5)P2, suggesting that Gag sensitivity to PI(4,5)P2 acyl chain saturation is determined directly by the matrix-PI(4,5)P2 interaction, rather

  13. In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.

    PubMed

    Bulley, Simon J; Droubi, Alaa; Clarke, Jonathan H; Anderson, Karen E; Stephens, Len R; Hawkins, Phillip T; Irvine, Robin F

    2016-09-20

    Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly effect" described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131-1136], whereby through apparently the same underlying mechanism, the removal of a protein's activity from a cell can have widely divergent effects depending on the time course of that removal. PMID:27601656

  14. Incorporating root hydraulic redistribution in CLM4.5: Effects on predicted site and global evapotranspiration, soil moisture, and water storage

    NASA Astrophysics Data System (ADS)

    Tang, Jinyun; Riley, William J.; Niu, Jie

    2015-12-01

    We implemented the Amenu-Kumar model in the Community Land Model (CLM4.5) to simulate plant Root Hydraulic Redistribution (RHR) and analyzed its influence on CLM hydrology from site to global scales. We evaluated two numerical implementations: the first solved the coupled equations of root and soil water transport concurrently, while the second solved the two equations sequentially. Through sensitivity analysis, we demonstrate that the sequentially coupled implementation (SCI) is numerically incorrect, whereas the tightly coupled implementation (TCI) is numerically robust with numerical time steps varying from 1 to 30 min. At the site-level, we found the SCI approach resulted in better agreement with measured evapotranspiration (ET) at the AmeriFlux Blodgett Forest site, California, whereas the two approaches resulted in equally poor agreement between predicted and measured ET at the LBA Tapajos KM67 Mature Forest site in Amazon, Brazil. Globally, the SCI approach overestimated annual land ET by as much as 3.5 mm d-1 in some grid cells when compared to the TCI estimates. These comparisons demonstrate that TCI is a more robust numerical implementation of RHR. However, we found, even with TCI, that incorporating RHR resulted in worse agreement with measured soil moisture at both the Blodgett Forest and Tapajos sites and degraded the agreement between simulated terrestrial water storage anomaly and Gravity Recovery and Climate Experiment (GRACE) observations. We find including RHR in CLM4.5 improved ET predictions compared with the FLUXNET-MTE estimates north of 20° N but led to poorer predictions in the tropics. The biases in ET were robust and significant regardless of the four different pedotransfer functions or of the two meteorological forcing data sets we applied. We also found that the simulated water table was unrealistically sensitive to RHR. Therefore, we contend that further structural and data improvements are warranted to improve the hydrological

  15. Combined measurement and modeling of the hydrological impact of hydraulic redistribution using CLM4.5 at eight AmeriFlux sites

    NASA Astrophysics Data System (ADS)

    Fu, Congsheng; Wang, Guiling; Goulden, Michael L.; Scott, Russell L.; Bible, Kenneth; Cardon, Zoe G.

    2016-05-01

    Effects of hydraulic redistribution (HR) on hydrological, biogeochemical, and ecological processes have been demonstrated in the field, but the current generation of standard earth system models does not include a representation of HR. Though recent studies have examined the effect of incorporating HR into land surface models, few (if any) have done cross-site comparisons for contrasting climate regimes and multiple vegetation types via the integration of measurement and modeling. Here, we incorporated the HR scheme of Ryel et al. (2002) into the NCAR Community Land Model Version 4.5 (CLM4.5), and examined the ability of the resulting hybrid model to capture the magnitude of HR flux and/or soil moisture dynamics from which HR can be directly inferred, to assess the impact of HR on land surface water and energy budgets, and to explore how the impact may depend on climate regimes and vegetation conditions. Eight AmeriFlux sites with contrasting climate regimes and multiple vegetation types were studied, including the Wind River Crane site in Washington State, the Santa Rita Mesquite savanna site in southern Arizona, and six sites along the Southern California Climate Gradient. HR flux, evapotranspiration (ET), and soil moisture were properly simulated in the present study, even in the face of various uncertainties. Our cross-ecosystem comparison showed that the timing, magnitude, and direction (upward or downward) of HR vary across ecosystems, and incorporation of HR into CLM4.5 improved the model-measurement matches of evapotranspiration, Bowen ratio, and soil moisture particularly during dry seasons. Our results also reveal that HR has important hydrological impact in ecosystems that have a pronounced dry season but are not overall so dry that sparse vegetation and very low soil moisture limit HR.

  16. Combined measurement and modeling of the hydrological impact of hydraulic redistribution using CLM4.5 at eight AmeriFlux sites

    DOE PAGES

    Fu, Congsheng; Wang, Guiling; Goulden, Michael L.; Scott, Russell L.; Bible, Kenneth; G. Cardon, Zoe

    2016-05-17

    Effects of hydraulic redistribution (HR) on hydrological, biogeochemical, and ecological processes have been demonstrated in the field, but the current generation of standard earth system models does not include a representation of HR. Though recent studies have examined the effect of incorporating HR into land surface models, few (if any) have done cross-site comparisons for contrasting climate regimes and multiple vegetation types via the integration of measurement and modeling. Here, we incorporated the HR scheme of Ryel et al. (2002) into the NCAR Community Land Model Version 4.5 (CLM4.5), and examined the ability of the resulting hybrid model to capture themore » magnitude of HR flux and/or soil moisture dynamics from which HR can be directly inferred, to assess the impact of HR on land surface water and energy budgets, and to explore how the impact may depend on climate regimes and vegetation conditions. Eight AmeriFlux sites with contrasting climate regimes and multiple vegetation types were studied, including the Wind River Crane site in Washington State, the Santa Rita Mesquite savanna site in southern Arizona, and six sites along the Southern California Climate Gradient. HR flux, evapotranspiration (ET), and soil moisture were properly simulated in the present study, even in the face of various uncertainties. Our cross-ecosystem comparison showed that the timing, magnitude, and direction (upward or downward) of HR vary across ecosystems, and incorporation of HR into CLM4.5 improved the model-measurement matches of evapotranspiration, Bowen ratio, and soil moisture particularly during dry seasons. Lastly, our results also reveal that HR has important hydrological impact in ecosystems that have a pronounced dry season but are not overall so dry that sparse vegetation and very low soil moisture limit HR.« less

  17. CHARACTERIZATION AND NUCLEOTIDE SEQUENCE DETERMINATION OF A REPEAT ELEMENT ISOLATED FROM A 2,4,5,-T DEGRADING STRAIN OF PSEUDOMONAS CEPACIA

    EPA Science Inventory

    Pseudomonas cepacia strain AC1100, capable of growth on 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), was mutated to the 2,4,5-T− strain PT88 by a ColE1 :: Tn5 chromosomal insertion. Using cloned DNA from the region flanking the insertion, a 1477-bp sequence (designated RS1100) wa...

  18. BIODEGRATION OF 2,4,5-TRICHLOROPHENOXYACETIC ACID IN LIQUID CULTURE AND IN SOIL BY THE WHITE ROT FUNGUS PHANEROCHAETE CHRYSOSPORIUM

    EPA Science Inventory

    Extensive biodegradation of [14C]-2,4,5-trichlorophenoxyacetic acid ([[14C]-2,4,5-T) by the white rot fungus Phanerochaete chrysosporium was demonstrated in nutrient nitrogen-limited aqueous cultures and in [14C]-2,4,5-T-contaminated soil inoculat...

  19. New polyfunctional imidazo[4,5-C]pyridine motifs: synthesis, crystal studies, docking studies and antimicrobial evaluation.

    PubMed

    Jose, Gilish; Suresha Kumara, T H; Nagendrappa, Gopalpur; Sowmya, H B V; Jasinski, Jerry P; Millikan, Sean P; Chandrika, N; More, Sunil S; Harish, B G

    2014-04-22

    New antimicrobial agents, imidazo[4,5-c]pyridine derivatives have been synthesized. We have developed a new synthetic protocol for the final reaction, an efficient microwave-assisted synthesis of imidazo[4,5-c]pyridines from substituted 3,4-diaminopyridine and carboxylic acids in presence of DBU mediated by T3P. The chemical structures of the new compounds were characterized by IR, (1)H NMR, (13)C NMR, mass spectral analysis and elemental analysis. In addition, single crystal X-ray diffraction has also been recorded for compound 9c. The in vitro antimicrobial activities of the compounds were conducted against various Gram-negative, Gram-positive bacteria and fungi. Amongst the tested compounds 9c, 9e, 9g, 9k and 9l displayed promising antimicrobial activity. The molecular docking of GlcN-6-P synthase with newly synthesized compounds was carried out.

  20. An Efficient Solution-Phase Synthesis of 4,5,7-Trisubstituted Pyrrolo[3,2-d]pyrimidines

    PubMed Central

    Zhang, Weihe; Liu, Jing; Stashko, Michael A.; Wang, Xiaodong

    2013-01-01

    We have developed an efficient and robust route to synthesize 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines as potent kinase inhibitors. This solution-phase synthesis features a SNAr substitution reaction, cross-coupling reaction, one-pot reduction/reductive amination and N-alkylation reaction. These reactions occur rapidly with high yields and have broad substrate scopes. A variety of groups can be selectively introduced into the N5 and C7 positions of 4,5,7-trisubstituted pyrrolopyrimidines at a late stage of the synthesis, thereby providing a highly efficient approach to explore the structure-activity relationships of pyrrolopyrimidine derivatives. Four synthetic analogs have been profiled against a panel of 48 kinases and a new and selective FLT3 inhibitor 9 is identified. PMID:23181516