Science.gov

Sample records for 7-8 times higher

  1. Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

    PubMed Central

    El-Ela, Mostafa Abou; El-Komy, Mohamed; Hay, Rania Abdel; Hegazy, Rehab; Sharobim, Amin; Rashed, Laila; Amr, Khalda

    2017-01-01

    Background Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. Methods Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. Results This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). Conclusions TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR. PMID:28192646

  2. Progress in reducing aerodynamic drag for higher efficiency of heavy duty trucks (class 7-8)

    SciTech Connect

    Brady, M; Browand, F; Hammache, M; Heineck, J T; Leonard, A; McCallen, R; Ross, J; Rutledge, W; Salari, K; Storms, B

    1999-04-01

    This paper describes research and development for reducing the aerodynamic drag of heavy vehicles by demonstrating new approaches for the numerical simulation and analysis of aerodynamic flow. In addition, greater use of newly developed computational tools holds promise for reducing the number of prototype tests, for cutting manufacturing costs, and for reducing overall time to market. Experimental verification and validation of new computational fluid dynamics methods are also an important part of this approach. Experiments on a model of an integrated tractor-trailer are underway at NASA Ames Research Center and the University of Southern California. Companion computer simulations are being performed by Sandia National Laboratories, Lawrence Livermore National Laboratory, and California Institute of Technology using state-of-the-art techniques, with the intention of implementing more complex methods in the future.

  3. Progress in Reducing Aerodynamic Drag for Higher Efficiency of Heavy Duty Trucks (Class 7-8)

    SciTech Connect

    Rose McCallen; Richard Couch; Juliana Hsu; Fred Browand; Mustapha Hammache; Anthony Leonard; Mark Brady; Kambiz Salari; Walter Rutledge; James Ross; Bruce Storms; J.T. Heineck; David Driver; James Bell; Gregory Zilliac

    1999-12-31

    This paper describes research and development for reducing the aerodynamic drag of heavy vehicles by demonstrating new approaches for the numerical simulation and analysis of aerodynamic flow. In addition, greater use of newly developed computational tools holds promise for reducing the number of prototype tests, for cutting manufacturing costs, and for reducing overall time to market. Experimental verification and validation of new computational fluid dynamics methods are also an important part of this approach. Experiments on a model of an integrated tractor-trailer are underway at NASA Ames Research Center and the University of Southern California. Companion computer simulations are being performed by Sandia National Laboratories, Lawrence Livermore National Laboratory, and California Institute of Technology using state-of-the-art techniques, with the intention of implementing more complex methods in the future.

  4. 41 CFR 302-7.8 - Is there a time limit for the temporary storage of an authorized HHG shipment?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT (PBP&E) General Rules § 302-7.8 Is there a time limit for the temporary storage of an...

  5. 41 CFR 302-7.8 - Is there a time limit for the temporary storage of an authorized HHG shipment?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT (PBP&E) General Rules § 302-7.8 Is there a time limit for the temporary storage of an...

  6. GPS constraints on M 7-8 earthquake recurrence times for the New Madrid seismic zone

    USGS Publications Warehouse

    Stuart, W.D.

    2001-01-01

    Newman et al. (1999) estimate the time interval between the 1811-1812 earthquake sequence near New Madrid, Missouri and a future similar sequence to be at least 2,500 years, an interval significantly longer than other recently published estimates. To calculate the recurrence time, they assume that slip on a vertical half-plane at depth contributes to the current interseismic motion of GPS benchmarks. Compared to other plausible fault models, the half-plane model gives nearly the maximum rate of ground motion for the same interseismic slip rate. Alternative models with smaller interseismic fault slip area can satisfy the present GPS data by having higher slip rate and thus can have earthquake recurrence times much less than 2,500 years.

  7. Real-Time seismic waveforms monitoring with BeiDou Navigation Satellite System (BDS) observations for the 2015 Mw 7.8 Nepal earthquake

    NASA Astrophysics Data System (ADS)

    Geng, T.

    2015-12-01

    Nowadays more and more high-rate Global Navigation Satellite Systems (GNSS) data become available in real time, which provide more opportunities to monitor the seismic waveforms. China's GNSS, BeiDou Navigation Satellite System (BDS), has already satisfied the requirement of stand-alone precise positioning in Asia-Pacific region with 14 in-orbit satellites, which promisingly suggests that BDS could be applied to the high-precision earthquake monitoring as GPS. In the present paper, real-time monitoring of seismic waveforms using BDS measurements is assessed. We investigate a so-called "variometric" approach to measure real-time seismic waveforms with high-rate BDS observations. This approach is based on time difference technique and standard broadcast products which are routinely available in real time. The 1HZ BDS data recorded by Beidou Experimental Tracking Stations (BETS) during the 2015 Mw 7.8 Nepal earthquake is analyzed. The results indicate that the accuracies of velocity estimation from BDS are 2-3 mm/s in horizontal components and 8-9 mm/s in vertical component, respectively, which are consistent with GPS. The seismic velocity waveforms during earthquake show good agreement between BDS and GPS. Moreover, the displacement waveforms is reconstructed by an integration of velocity time series with trend removal. The displacement waveforms with the accuracy of 1-2 cm are derived by comparing with post-processing GPS precise point positioning (PPP).

  8. Real-time capture of seismic waves using high-rate multi-GNSS observations: Application to the 2015 Mw 7.8 Nepal earthquake

    NASA Astrophysics Data System (ADS)

    Geng, Tao; Xie, Xin; Fang, Rongxin; Su, Xing; Zhao, Qile; Liu, Gang; Li, Heng; Shi, Chuang; Liu, Jingnan

    2016-01-01

    The variometric approach is investigated to measure real-time seismic waves induced by the 2015 Mw 7.8 Nepal earthquake with high-rate multi-GNSS observations, especially with the contribution of newly available BDS. The velocity estimation using GPS + BDS shows an additional improvement of around 20% with respect to GPS-only solutions. We also reconstruct displacements by integrating GNSS-derived velocities after a linear trend removal (IGV). The displacement waveforms with accuracy of better than 5 cm are derived when postprocessed GPS precise point positioning results are used as ground truth, even if those stations have strong ground motions and static offsets of up to 1-2 m. GNSS-derived velocity and displacement waveforms with the variometric approach are in good agreement with results from strong motion data. We therefore conclude that it is feasible to capture real-time seismic waves with multi-GNSS observations using the IGV-enhanced variometric approach, which has critical implications for earthquake early warning, tsunami forecasting, and rapid hazard assessment.

  9. Real-Time Science on Social Media: The Example of Twitter in the Minutes, Hours, Days after the 2015 M7.8 Nepal Earthquake

    NASA Astrophysics Data System (ADS)

    Lomax, A.; Bossu, R.; Mazet-Roux, G.

    2015-12-01

    Scientific information on disasters such as earthquakes typically comes firstly from official organizations, news reports and interviews with experts, and later from scientific presentations and peer-reviewed articles. With the advent of the Internet and social media, this information is available in real-time from automated systems and within a dynamic, collaborative interaction between scientific experts, responders and the public. After the 2015 M7.8 Nepal earthquake, Twitter Tweets from earth scientists* included information, analysis, commentary and discussion on earthquake parameters (location, size, mechanism, rupture extent, high-frequency radiation, …), earthquake effects (distribution of felt shaking and damage, triggered seismicity, landslides, …), earthquake rumors (e.g. the imminence of a larger event) and other earthquake information and observations (aftershock forecasts, statistics and maps, source and regional tectonics, seismograms, GPS, InSAR, photos/videos, …).In the future (while taking into account security, false or erroneous information and identity verification), collaborative, real-time science on social media after a disaster will give earlier and better scientific understanding and dissemination of public information, and enable improved emergency response and disaster management.* A sample of scientific Tweets after the 2015 Nepal earthquake: In the first minutes: "mb5.9 Mwp7.4 earthquake Nepal 2015.04.25-06:11:25UTC", "Major earthquake shakes Nepal 8 min ago", "Epicenter between Pokhara and Kathmandu", "Major earthquake shakes Nepal 18 min ago. Effects derived from witnesses' reports". In the first hour: "shallow thrust faulting to North under Himalayas", "a very large and shallow event ... Mw7.6-7.7", "aftershocks extend east and south of Kathmandu, so likely ruptured beneath city", "Valley-blocking landslides must be a very real worry". In the first day: "M7.8 earthquake in Nepal 2hr ago: destructive in Kathmandu Valley and

  10. Ultrafast photodynamics of pyrazine in the vacuum ultraviolet region studied by time-resolved photoelectron imaging using 7.8-eV pulses

    NASA Astrophysics Data System (ADS)

    Horio, Takuya; Suzuki, Yoshi-ichi; Suzuki, Toshinori

    2016-07-01

    The ultrafast electronic dynamics of pyrazine (C4N2H4) were studied by time-resolved photoelectron imaging (TRPEI) using the third (3ω, 4.7 eV) and fifth harmonics (5ω, 7.8 eV) of a femtosecond Ti:sapphire laser (ω). Although the photoionization signals due to the 5ω - 3ω and 3ω - 5ω pulse sequences overlapped near the time origin, we have successfully extracted their individual TRPEI signals using least squares fitting of the observed electron kinetic energy distributions. When the 5ω pulses preceded the 3ω pulses, the 5ω pulses predominantly excited the S4 (ππ*, 1B1u+1B2u) state. The photoionization signal from the S4 state generated by the time-delayed 3ω pulses was dominated by the D3(2B2g)←S4 photoionization process and exhibited a broad electron kinetic energy distribution, which rapidly downshifted in energy within 100 fs. Also observed were the photoionization signals for the 3s, 3pz, and 3py members of the Rydberg series converging to D0(2Ag). The Rydberg signals appeared immediately within our instrumental time resolution of 27 fs, indicating that these states are directly photoexcited from the ground state or populated from S4 within 27 fs. The 3s, 3pz, and 3py states exhibited single exponential decay with lifetimes of 94 ± 2, 89 ± 2, and 58 ± 1 fs, respectively. With the reverse pulse sequence of 3ω - 5ω, the ultrafast internal conversion (IC) from S2(ππ*) to S1(nπ*) was observed. The decay associated spectrum of S2 exhibited multiple bands ascribed to D0, D1, and D3, in agreement with the 3ω-pump and 6ω-probe experiment described in our preceding paper [T. Horio et al., J. Chem. Phys. 145, 044306 (2016)]. The electron kinetic energy and angular distributions from S1 populated by IC from S2 are also discussed.

  11. The Renaissance. Grade 7 Model Lesson for Standard 7.8. World History and Geography: Medieval and Early Modern Times. California History-Social Science Course Models.

    ERIC Educational Resources Information Center

    Zachlod, Michelle, Ed.

    California State Standard 7.8 is delineated in the following manner: "Students analyze the origins, accomplishments, and diffusion of the Renaissance," in terms of the way in which the revival of classical learning and the arts affected a new interest in humanism; the importance of Florence in the early stages of the Renaissance and the…

  12. Higher Education for Our Time

    ERIC Educational Resources Information Center

    Burnett, Dana D.; Collins, Natalia D.

    2010-01-01

    Public higher education is currently experiencing a decline in financial support from state governments, an acceleration of enrollment growth, and a shift from a transformational to a transactional student relationship. Private institutions are also struggling with increasing operational costs, and decreases in revenue from endowments and…

  13. Part Time Study in Higher Education.

    ERIC Educational Resources Information Center

    Neville, Colin

    This document, which is intended for adults considering enrolling in part-time study in higher education, examines the objectives and experiences of adults who have pursued part-time study in higher education in the United Kingdom. The following reasons why adults return to higher education are discussed: personal development; self-fulfillment;…

  14. Higher Education: A Time for Triage?

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1995-10-01

    Higher education faces unprecedented challenges. The confluence of changing economic and demographic tends; new patterns of federal and state spending; more explicit expectations by students and their families for affordable, accessible education; and heightened scrutiny by those who claim a legitimate interest in higher education is inescapably altering the environment in which this system operates. Higher education will never again be as it was before. Further, many believe that tinkering around the margins is no longer an adequate response to the new demands. Fundamental change is deemed necessary to meet the challenge of this melange of pressures. A number of commentators have observed that political and corporate America have responded to their challenges by instituting a fundamental restructuring of those institutions. The medical community is also in the midst of a similar basic restructuring of the health care delivery system in this country. Now its education's turn. People are questioning the historically expressed mission of higher education. They make the claim that we cost too much, spend carelessly, teach poorly, plan myopically, and when questioned, act defensively. Educational administrators, from department chairs up, are confronted with the task of simultaneously reforming and cutting back. They have no choice. They must establish politically sophisticated priority settings and effect a hard-nosed reallocation of resources in a social environment where competing public needs have equivalent--or stronger--emotional pulls. Triage in a medical context involves confronting an emergency in which the demand for attention far outstrips available assistance by establishing a sequence of care in which one key individual orchestrates the application of harsh priorities which have been designed to maximize the number of survivors. In recent years, the decisions that have been made in some centers of higher education bear a striking similarity. The literature

  15. 7,8-Secolignans from the fruits of Schisandra neglecta.

    PubMed

    Wang, Huan; Yang, Juan-Xia; Lou, Jie; Liu, Gui-You; Li, Li-Mei; Sun, Han-Dong; Xiao, Wei-Lie; Hu, Qiu-Fen; Gao, Xue-Mei

    2015-01-01

    Two new 7,8-secolignans, neglectahenols E and F (1 and 2), together with four known 7,8-secolignans (3-6), were isolated from the fruits of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activities at the concentration of 20 μM. Compounds 1 and 6 showed high anti-TMV activities with inhibition rates of 38.2% and 32.7%, respectively. These rates are higher than that of a positive control. Compounds 2-5 also showed modest anti-TMV activities with inhibition rates in the range of 22.8-28.7%. These rates are close to that of a positive control.

  16. Representing 30 Years of Higher Education Change: UK Universities and the "Times Higher"

    ERIC Educational Resources Information Center

    Gewirtz, Sharon; Cribb, Alan

    2013-01-01

    This paper argues that the "Times Higher" provides a powerful tool for understanding the changing character of UK higher education (HE) and can usefully be seen as representative, and in some ways constitutive, of that changing character. Drawing on an analysis of a sample of stories from the "Times Higher," it documents the…

  17. RDamage 6, 7, 8 & 9 Cassettes

    SciTech Connect

    Griego, Jeffrey R; Kaul, Ann

    2012-06-08

    The RDamage series of ten experiments is part of a long-term collaboration with RFNC/VNIIEF in pulsed power technology. These experiments use a cylindrical configuration to study spallation damage, which allows for a natural recollection of the damaged material under proper driving conditions and post-shot collection of the damaged target material for subsequent metallographic analysis. Dynamic insitu experimental velocimetry diagnostics are also employed. LANL is responsible for the design of the experimental load and velocimetry system. VNIIEF is responsible for the design and construction of the driving explosive magnetic generator. In the RDamage-0, -1 and -2 experiments, data was collected about failure initiation of a well-characterized material (aluminum) in a cylindrical geometry. The RDamage-3, -4 and -5 experiments produced data on the behavior of material recollected after damage from pressures in the damage initiation regime. Data on the behavior of material recollected after complete failure was collected in the RDamage-6, -7, -8 and -9 experiments. This presentation shows the evolution of the load assembly through the experimental series.

  18. Just in Time Research: Data Breaches in Higher Education

    ERIC Educational Resources Information Center

    Grama, Joanna

    2014-01-01

    This "Just in Time" research is in response to recent discussions on the EDUCAUSE Higher Education Information Security Council (HEISC) discussion list about data breaches in higher education. Using data from the Privacy Rights Clearinghouse, this research analyzes data breaches attributed to higher education. The results from this…

  19. Part-Time Higher Education: Employer Engagement under Threat?

    ERIC Educational Resources Information Center

    Mason, Geoff

    2014-01-01

    Employer support for employees who are studying part-time for higher education qualifications constitutes a form of indirect employer engagement with higher education institutions that has contributed strongly to the development of work-related skills and knowledge over the years. However, this form of employer engagement with higher education…

  20. 10 CFR 7.8 - Charter filing requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Charter filing requirements. 7.8 Section 7.8 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.8 Charter filing requirements. No advisory committee... Works of the United States Senate and the Committee on Energy and Commerce of the United States House...

  1. 10 CFR 7.8 - Charter filing requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Charter filing requirements. 7.8 Section 7.8 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.8 Charter filing requirements. No advisory committee... Works of the United States Senate and the Committee on Energy and Commerce of the United States House...

  2. 10 CFR 7.8 - Charter filing requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Charter filing requirements. 7.8 Section 7.8 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.8 Charter filing requirements. No advisory committee... Works of the United States Senate and the Committee on Energy and Commerce of the United States House...

  3. 10 CFR 7.8 - Charter filing requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Charter filing requirements. 7.8 Section 7.8 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.8 Charter filing requirements. No advisory committee... Works of the United States Senate and the Committee on Energy and Commerce of the United States House...

  4. 10 CFR 7.8 - Charter filing requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Charter filing requirements. 7.8 Section 7.8 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.8 Charter filing requirements. No advisory committee... Works of the United States Senate and the Committee on Energy and Commerce of the United States House...

  5. 7 CFR 7.8 - Conduct of community committee elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Conduct of community committee elections. 7.8 Section 7.8 Agriculture Office of the Secretary of Agriculture SELECTION AND FUNCTIONS OF AGRICULTURAL STABILIZATION AND CONSERVATION STATE, COUNTY AND COMMUNITY COMMITTEES § 7.8 Conduct of community...

  6. 45 CFR 7.8 - Employee's right of appeal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Employee's right of appeal. 7.8 Section 7.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.8 Employee's right of appeal. An employee who is aggrieved by a determination of the Department may appeal to the Commissioner of Patents, pursuant...

  7. A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect

    PubMed Central

    Liu, Xia; Chan, Chi-Bun; Jang, Sung-Wuk; Pradoldej, Sompol; Huang, Junjian; He, Kunyan; Phun, Lien H.; France, Stefan; Xiao, Ge; Jia, Yonghui; Luo, Hongbo R.; Ye, Keqiang

    2011-01-01

    7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin-receptor-kinase B (TrkB) agonist. Our preliminary structural activity relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for the agonistic effect. To improve the lead compound's agonistic activity, we have conducted an extensive SAR study and synthesized numerous derivatives. We have successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays higher TrkB agonistic activity than the lead. This novel compound also exhibits a more robust and longer TrkB activation effect in animals. Consequently, this new compound reveals more potent anti-apoptotic activity. Interestingly, chronic oral administration of 4'-dimethylamino-7,8-dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and demonstrates marked antidepressant effects. Hence, our data support that the synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally bioavailable TrkB agonists and possess potent antidepressant effects. PMID:21073191

  8. The Times Higher Education Ranking Product: Visualising Excellence through Media

    ERIC Educational Resources Information Center

    Stack, Michelle L.

    2013-01-01

    This paper will examine the Times Higher Education's (THE) World University Rankings as a corporate media product. A number of empirical studies have critiqued the methodology of the THE, yet individuals, Higher Education Institutions (HEIs) and governments continue to use them for decision-making. This paper analyses the influence of…

  9. Higher Education in Recessionary Times: A UK Colloquium

    ERIC Educational Resources Information Center

    Evans, Mary

    2010-01-01

    This article talks about a meeting on "Higher Education in Recessionary Times" on March 24, 2010, which was hosted by the Society for Higher Education Research Policy Network. Although the meeting did take place in the context of an expected General Election, and on budget day, there was a general sense on the day that whoever won the…

  10. Adopting Consumer Time: Potential Issues for Higher Education

    ERIC Educational Resources Information Center

    Gibbs, Paul

    2009-01-01

    Time and temporality have received little attention in the consumerism, marketing or, until recently, higher education literature. This paper attempts to compare the notions of timing implicit in education as "paideia" (transitional personal growth) with that implicit in consumerism and the marketing practices which foster it. This…

  11. Quantum Theory of Antisymmetric Higher Rank Tensor Gauge Field in Higher Dimensional Space-Time

    NASA Astrophysics Data System (ADS)

    Kimura, T.

    1981-01-01

    In a higher dimensional space-time, the Lagrangian formalism and the canonical operator formalism of covariant quantization of the antisymmetric tensor gauge field of higher rank are formulated consistently by introducing BRS transformation and Lagrangian multiplier fields From the effective Lagrangian, the numbers of the physical components and the effective ghosts are counted correctly without referring to a special reference frame. The confinement of unphysical components is assured from the viewpoint of the ``quartet mechanism'' of Kugo and Ojima.

  12. Does the Timing of Tracking Affect Higher Education Completion?

    ERIC Educational Resources Information Center

    van Elk, Roel; van der Steeg, Marc; Webbink, Dinand

    2011-01-01

    This paper investigates the effect of the timing of tracking on completion of higher education by exploiting unique variation from the Dutch education system. At the age of 12 Dutch students can enrol in tracked schools or in comprehensive schools. The comprehensive schools postpone enrolment into tracked classes by one or two years. OLS- and…

  13. Naked singularities in higher dimensional Vaidya space-times

    SciTech Connect

    Ghosh, S. G.; Dadhich, Naresh

    2001-08-15

    We investigate the end state of the gravitational collapse of a null fluid in higher-dimensional space-times. Both naked singularities and black holes are shown to be developing as the final outcome of the collapse. The naked singularity spectrum in a collapsing Vaidya region (4D) gets covered with the increase in dimensions and hence higher dimensions favor a black hole in comparison to a naked singularity. The cosmic censorship conjecture will be fully respected for a space of infinite dimension.

  14. Wormhole in higher-dimensional space-time

    NASA Astrophysics Data System (ADS)

    Shinkai, Hisa-aki; Torii, Takashi

    2015-04-01

    We introduce our recent studies on wormhole, especially its stability aspect in higher-dimensional space-time both in general relativity and in Gauss-Bonnet gravity. We derived the Ellis-type wormhole solution in n-dimensional general relativity, and found existence of an unstable mode in its linear perturbation analysis. We also evolved it numerically in dualnullcoordinate system, and confirmed its instability. The wormhole throat will change into black hole horizons for the input of the (relatively) positive energy, while it will change into inflationary expansion for the (relatively) negative energy input. If we add Gauss-Bonnet terms (higher curvature correction terms in gravity), then wormhole tends to expand (or change to black hole) if the coupling constant α is positive (negative), and such bifurcation of the throat horizon is observed earlier in higher dimension.

  15. Efficient multiple time-stepping algorithms of higher order

    NASA Astrophysics Data System (ADS)

    Demirel, Abdullah; Niegemann, Jens; Busch, Kurt; Hochbruck, Marlis

    2015-03-01

    Multiple time-stepping (MTS) algorithms allow to efficiently integrate large systems of ordinary differential equations, where a few stiff terms restrict the timestep of an otherwise non-stiff system. In this work, we discuss a flexible class of MTS techniques, based on multistep methods. Our approach contains several popular methods as special cases and it allows for the easy construction of novel and efficient higher-order MTS schemes. In addition, we demonstrate how to adapt the stability contour of the non-stiff time-integration to the physical system at hand. This allows significantly larger timesteps when compared to previously known multistep MTS approaches. As an example, we derive novel predictor-corrector (PCMTS) schemes specifically optimized for the time-integration of damped wave equations on locally refined meshes. In a set of numerical experiments, we demonstrate the performance of our scheme on discontinuous Galerkin time-domain (DGTD) simulations of Maxwell's equations.

  16. Programming real-time executives in higher order language

    NASA Technical Reports Server (NTRS)

    Foudriat, E. C.

    1982-01-01

    Methods by which real-time executive programs can be implemented in a higher order language are discussed, using HAL/S and Path Pascal languages as program examples. Techniques are presented by which noncyclic tasks can readily be incorporated into the executive system. Situations are shown where the executive system can fail to meet its task scheduling and yet be able to recover either by rephasing the clock or stacking the information for later processing. The concept of deadline processing is shown to enable more effective mixing of time and information synchronized systems.

  17. A higher-order Robert-Asselin type time filter

    NASA Astrophysics Data System (ADS)

    Li, Yong; Trenchea, Catalin

    2014-02-01

    The Robert-Asselin (RA) time filter combined with leapfrog scheme is widely used in numerical models of weather and climate. It successfully suppresses the spurious computational mode associated with the leapfrog method, but it also weakly dampens the physical mode and degrades the numerical accuracy. The Robert-Asselin-Williams (RAW) time filter is a modification of the RA filter that reduces the undesired numerical damping of RA filter and increases the accuracy. We propose a higher-order Robert-Asselin (hoRA) type time filter which effectively suppresses the computational modes and achieves third-order accuracy with the same storage requirement as RAW filter. Like RA and RAW filters, the hoRA filter is non-intrusive, and so it would be easily implementable. The leapfrog scheme with hoRA filter is almost as accurate, stable and efficient as the intrusive third-order Adams-Bashforth (AB3) method.

  18. Higher order time integration methods for two-phase flow

    NASA Astrophysics Data System (ADS)

    Kees, Christopher E.; Miller, Cass T.

    Time integration methods that adapt in both the order of approximation and time step have been shown to provide efficient solutions to Richards' equation. In this work, we extend the same method of lines approach to solve a set of two-phase flow formulations and address some mass conservation issues from the previous work. We analyze these formulations and the nonlinear systems that result from applying the integration methods, placing particular emphasis on their index, range of applicability, and mass conservation characteristics. We conduct numerical experiments to study the behavior of the numerical models for three test problems. We demonstrate that higher order integration in time is more efficient than standard low-order methods for a variety of practical grids and integration tolerances, that the adaptive scheme successfully varies the step size in response to changing conditions, and that mass balance can be maintained efficiently using variable-order integration and an appropriately chosen numerical model formulation.

  19. 45 CFR 7.8 - Employee's right of appeal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.8 Employee... Executive Order 10930, and regulations issued thereunder, by filing a written appeal with the Commissioner... receiving written notice of such determination....

  20. Full-Time Students? Term-Time Employment among Higher Education Students in Ireland

    ERIC Educational Resources Information Center

    Darmody, Merike; Smyth, Emer

    2008-01-01

    A good deal of research has focused on part-time employment among full-time students in higher education. However, little attention has been paid to the way in which these patterns may reflect societally specific processes rather than universal trends. This paper examines ways in which the higher education system itself can influence variation in…

  1. Too much noise in the Times Higher Education rankings.

    PubMed

    Bookstein, Fred L; Seidler, Horst; Fieder, Martin; Winckler, Georg

    2010-10-01

    Several individual indicators from the Times Higher Education Survey (THES) data base-the overall score, the reported staff-to-student ratio, and the peer ratings-demonstrate unacceptably high fluctuation from year to year. The inappropriateness of the summary tabulations for assessing the majority of the "top 200" universities would be apparent purely for reason of this obvious statistical instability regardless of other grounds of criticism. There are far too many anomalies in the change scores of the various indices for them to be of use in the course of university management.

  2. Synaptic contacts impaired by styrene-7,8-oxide toxicity

    SciTech Connect

    Corsi, P. D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

    2007-10-01

    Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity.

  3. Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys

    PubMed Central

    He, Jingjing; Xiang, Zheng; Zhu, Xiaoqing; Ai, Zongyong; Shen, Jingsong; Huang, Tianzhuang; Liu, Liegang; Ji, Weizhi; Li, Tianqing

    2016-01-01

    Parkinson’s disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys. The half-life time of 7, 8-DHF in monkey plasma is about 4–8 hrs. Furthermore, these monkeys maintain health state throughout the course of seven-month treatments of 7, 8-DHF (30 mg/kg/day). Importantly, 7, 8-DHF treatments can prevent the progressive degeneration of midbrain dopaminergic neurons by attenuating neurotoxic effects of MPP+ and display strong neuroprotective effects in monkeys. Our study demonstrates that this promising small molecule may be transited into a clinical useful pharmacological agent. PMID:27731318

  4. Improved Continuous-Time Higher Harmonic Control Using Hinfinity Methods

    NASA Astrophysics Data System (ADS)

    Fan, Frank H.

    The helicopter is a versatile aircraft that can take-off and land vertically, hover efficiently, and maneuver in confined space. This versatility is enabled by the main rotor, which also causes undesired harmonic vibration during operation. This unwanted vibration has a negative impact on the practicality of the helicopter and also increases its operational cost. Passive control techniques have been applied to helicopter vibration suppression, but these methods are generally heavy and are not robust to changes in operating conditions. Feedback control offers the advantages of robustness and potentially higher performance over passive control techniques, and amongst the various feedback schemes, Shaw's higher harmonic control algorithm has been shown to be an effective method for attenuating harmonic disturbance in helicopters. In this thesis, the higher harmonic disturbance algorithm is further developed to achieve improved performance. One goal in this thesis is to determine the importance of periodicity in the helicopter rotor dynamics for control synthesis. Based on the analysis of wind tunnel data and simulation results, we conclude the helicopter rotor can be modeled reasonably well as linear and time-invariant for control design purposes. Modeling the helicopter rotor as linear time-invariant allows us to apply linear control theory concepts to the higher harmonic control problem. Another goal in this thesis is to find the limits of performance in harmonic disturbance rejection. To achieve this goal, we first define the metrics to measure the performance of the controller in terms of response speed and robustness to changes in the plant dynamics. The performance metrics are incorporated into an Hinfinity control problem. For a given plant, the resulting Hinfinity controller achieves the maximum performance, thus allowing us to identify the performance limitation in harmonic disturbance rejection. However, the Hinfinity controllers are of high order, and may

  5. Pulse transmission transmitter including a higher order time derivate filter

    DOEpatents

    Dress, Jr., William B.; Smith, Stephen F.

    2003-09-23

    Systems and methods for pulse-transmission low-power communication modes are disclosed. A pulse transmission transmitter includes: a clock; a pseudorandom polynomial generator coupled to the clock, the pseudorandom polynomial generator having a polynomial load input; an exclusive-OR gate coupled to the pseudorandom polynomial generator, the exclusive-OR gate having a serial data input; a programmable delay circuit coupled to both the clock and the exclusive-OR gate; a pulse generator coupled to the programmable delay circuit; and a higher order time derivative filter coupled to the pulse generator. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.

  6. Polymer quantization, stability and higher-order time derivative terms

    NASA Astrophysics Data System (ADS)

    Cumsille, Patricio; Reyes, Carlos M.; Ossandon, Sebastian; Reyes, Camilo

    2016-03-01

    The possibility that fundamental discreteness implicit in a quantum gravity theory may act as a natural regulator for ultraviolet singularities arising in quantum field theory has been intensively studied. Here, along the same expectations, we investigate whether a nonstandard representation called polymer representation can smooth away the large amount of negative energy that afflicts the Hamiltonians of higher-order time derivative theories, rendering the theory unstable when interactions come into play. We focus on the fourth-order Pais-Uhlenbeck model which can be reexpressed as the sum of two decoupled harmonic oscillators one producing positive energy and the other negative energy. As expected, the Schrödinger quantization of such model leads to the stability problem or to negative norm states called ghosts. Within the framework of polymer quantization we show the existence of new regions where the Hamiltonian can be defined well bounded from below.

  7. Measuring Stratigraphic Congruence Across Trees, Higher Taxa, and Time

    PubMed Central

    O'Connor, Anne; Wills, Matthew A.

    2016-01-01

    The congruence between the order of cladistic branching and the first appearance dates of fossil lineages can be quantified using a variety of indices. Good matching is a prerequisite for the accurate time calibration of trees, while the distribution of congruence indices across large samples of cladograms has underpinned claims about temporal and taxonomic patterns of completeness in the fossil record. The most widely used stratigraphic congruence indices are the stratigraphic consistency index (SCI), the modified Manhattan stratigraphic measure (MSM*), and the gap excess ratio (GER) (plus its derivatives; the topological GER and the modified GER). Many factors are believed to variously bias these indices, with several empirical and simulation studies addressing some subset of the putative interactions. This study combines both approaches to quantify the effects (on all five indices) of eight variables reasoned to constrain the distribution of possible values (the number of taxa, tree balance, tree resolution, range of first occurrence (FO) dates, center of gravity of FO dates, the variability of FO dates, percentage of extant taxa, and percentage of taxa with no fossil record). Our empirical data set comprised 647 published animal and plant cladograms spanning the entire Phanerozoic, and for these data we also modeled the effects of mean age of FOs (as a proxy for clade age), the taxonomic rank of the clade, and the higher taxonomic group to which it belonged. The center of gravity of FO dates had not been investigated hitherto, and this was found to correlate most strongly with some measures of stratigraphic congruence in our empirical study (top-heavy clades had better congruence). The modified GER was the index least susceptible to bias. We found significant differences across higher taxa for all indices; arthropods had lower congruence and tetrapods higher congruence. Stratigraphic congruence—however measured—also varied throughout the Phanerozoic

  8. Measuring Stratigraphic Congruence Across Trees, Higher Taxa, and Time.

    PubMed

    O'Connor, Anne; Wills, Matthew A

    2016-09-01

    The congruence between the order of cladistic branching and the first appearance dates of fossil lineages can be quantified using a variety of indices. Good matching is a prerequisite for the accurate time calibration of trees, while the distribution of congruence indices across large samples of cladograms has underpinned claims about temporal and taxonomic patterns of completeness in the fossil record. The most widely used stratigraphic congruence indices are the stratigraphic consistency index (SCI), the modified Manhattan stratigraphic measure (MSM*), and the gap excess ratio (GER) (plus its derivatives; the topological GER and the modified GER). Many factors are believed to variously bias these indices, with several empirical and simulation studies addressing some subset of the putative interactions. This study combines both approaches to quantify the effects (on all five indices) of eight variables reasoned to constrain the distribution of possible values (the number of taxa, tree balance, tree resolution, range of first occurrence (FO) dates, center of gravity of FO dates, the variability of FO dates, percentage of extant taxa, and percentage of taxa with no fossil record). Our empirical data set comprised 647 published animal and plant cladograms spanning the entire Phanerozoic, and for these data we also modeled the effects of mean age of FOs (as a proxy for clade age), the taxonomic rank of the clade, and the higher taxonomic group to which it belonged. The center of gravity of FO dates had not been investigated hitherto, and this was found to correlate most strongly with some measures of stratigraphic congruence in our empirical study (top-heavy clades had better congruence). The modified GER was the index least susceptible to bias. We found significant differences across higher taxa for all indices; arthropods had lower congruence and tetrapods higher congruence. Stratigraphic congruence-however measured-also varied throughout the Phanerozoic, reflecting

  9. Time-resolved spectral imaging: better photon economy, higher accuracy

    NASA Astrophysics Data System (ADS)

    Fereidouni, Farzad; Reitsma, Keimpe; Blab, Gerhard A.; Gerritsen, Hans C.

    2015-03-01

    Lifetime and spectral imaging are complementary techniques that offer a non-invasive solution for monitoring metabolic processes, identifying biochemical compounds, and characterizing their interactions in biological tissues, among other tasks. Newly developed instruments that perform time-resolved spectral imaging can provide even more information and reach higher sensitivity than either modality alone. Here we report a multispectral lifetime imaging system based on a field-programmable gate array (FPGA), capable of operating at high photon count rates (12 MHz) per spectral detection channel, and with time resolution of 200 ps. We performed error analyses to investigate the effect of gate width and spectral-channel width on the accuracy of estimated lifetimes and spectral widths. Temporal and spectral phasors were used for analysis of recorded data, and we demonstrated blind un-mixing of the fluorescent components using information from both modalities. Fractional intensities, spectra, and decay curves of components were extracted without need for prior information. We further tested this approach with fluorescently doubly-labeled DNA, and demonstrated its suitability for accurately estimating FRET efficiency in the presence of either non-interacting or interacting donor molecules.

  10. Advancing Knowledge in Higher Education: Universities in Turbulent Times

    ERIC Educational Resources Information Center

    Fitzgerald, Tanya, Ed.

    2014-01-01

    Over the last three decades, higher education institutions have experienced massive changes. In particular, institutions of higher education have been positioned as a means to contribute to the knowledge economy and gain a level of competitive advantage in the global marketplace. "Advancing Knowledge in Higher Education: Universities in…

  11. 34 CFR 7.8 - Employee's right of appeal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.8 Employee's right of appeal. An... issued thereunder, by filing a written appeal with the Commissioner, in duplicate, and a copy of the..., fix in any case) after receiving written notice of such determination....

  12. Career Activities in Mathematics: Grades 7, 8, 9.

    ERIC Educational Resources Information Center

    Boise City Independent School District, ID.

    The career activities guide in mathematics, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates…

  13. Creating Sacred Places for Students in Grades 7&8.

    ERIC Educational Resources Information Center

    Fox, Sandra J.

    This guide attempts to help teachers of American Indian students in grades 7-8 provide a culturally relevant education that takes place in the regular classroom, includes content related to Indian students' lives, makes students proud, expands to other experiences, and enhances learning. Creating sacred places means responding appropriately to…

  14. Career Activities in Social Science: Grades 7, 8, 9.

    ERIC Educational Resources Information Center

    Boise City Independent School District, ID.

    The career activities guide in social science, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates…

  15. Career Activities in Language Arts: Grades 7, 8, 9.

    ERIC Educational Resources Information Center

    Boise City Independent School District, ID.

    The career activities guide in language arts, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates…

  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    Integrated Risk Information System (IRIS)

    2,3,7,8 - Tetrachlorodibenzo - p - dioxin ( TCDD ) ; CASRN 1746 - 01 - 6 This document has been provided for review to EPA scientists , interagency reviewers from other federal agencies and White House offices , and the public , and peer reviewed by independent scientists external to EPA . Sections

  17. Career Activities in Science: Grades 7, 8, 9.

    ERIC Educational Resources Information Center

    Boise City Independent School District, ID.

    The career activities guide in science, part of an Idaho State Department of Vocational Education career exploration series for grades 7, 8, and 9, is designed as supplementary material to enrich the regular curriculum. Any one activity in the guide might be used without involving any other activities. The cross-referenced index indicates grades,…

  18. 11 CFR 7.8 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Employees or Commissioners § 7.8 Gifts, entertainment, and favors. (a) A Commissioner or employee of the... affected by the performance or nonperformance of the Commissioner or employee's official duty. (b... persons concerned which are the motivating factors; (2) To the acceptance of food, refreshments,...

  19. 44 CFR 7.8 - Elementary and secondary schools.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Nondiscrimination in FEMA-Assisted Programs-General § 7.8 Elementary and secondary schools. The requirements of section 7 with respect to any elementary or secondary school or school system shall be deemed to be... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Elementary and...

  20. 44 CFR 7.8 - Elementary and secondary schools.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Nondiscrimination in FEMA-Assisted Programs-General § 7.8 Elementary and secondary schools. The requirements of section 7 with respect to any elementary or secondary school or school system shall be deemed to be... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Elementary and...

  1. 44 CFR 7.8 - Elementary and secondary schools.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Nondiscrimination in FEMA-Assisted Programs-General § 7.8 Elementary and secondary schools. The requirements of section 7 with respect to any elementary or secondary school or school system shall be deemed to be... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Elementary and...

  2. 44 CFR 7.8 - Elementary and secondary schools.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Nondiscrimination in FEMA-Assisted Programs-General § 7.8 Elementary and secondary schools. The requirements of section 7 with respect to any elementary or secondary school or school system shall be deemed to be... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Elementary and...

  3. 44 CFR 7.8 - Elementary and secondary schools.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Nondiscrimination in FEMA-Assisted Programs-General § 7.8 Elementary and secondary schools. The requirements of section 7 with respect to any elementary or secondary school or school system shall be deemed to be... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Elementary and...

  4. Alfvén wave in higher dimensional space time

    SciTech Connect

    Panigrahi, D.; Das, Ajanta; Chatterjee, S. E-mail: ajanta.das@heritageit.edu

    2009-09-01

    Following the wellknown spacetime decomposition technique as applied to (d+1) dimensions we write down the equations of magnetohydrodynamics (MHD) in a spatially flat generalised FRW universe. Assuming an equation of state for the background cosmic fluid we find solutions in turn for acoustic waves and also for Alfven waves in a warm (cold) magnetised plasma. Interestingly the different plasma modes closely resemble the flat space counterparts except that here the field variables all redshift with their time due to the expansion of the background. It is observed that in the ultrarelativistic limit the field parameters all scale as the free photon. The situation changes in the prerelativistic limit where the frequencies change in a bizarre fashion depending on initial conditions. It is observed that for a fixed magnetic field in a particular medium the Alfven wave velocity decreases with the number of dimensions, being the maximum in the usual 4D. Further for a fixed dimension the velocity attenuation is more significant in dust compared to the radiation era. We also find that in an expanding background the Alfven wave propagation is possible only in the high frequency range, determined by the strength of the external magnetic field, the mass density of the medium and also the dimensions of the spacetime. Further it is found that with expansion the cosmic magnetic field decays more sharply in higher dimensional cosmology, which is in line with observational demand.

  5. On the effect of cellular nucleophiles on the binding of metabolites of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene to nuclear DNA.

    PubMed

    Guenthner, T M; Jernström, B; Orrenius, S

    1980-05-01

    The binding to DNA of products resulting from the further activation of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene was studied in several incubation systems. In a system containing purified DNA and rat liver microsomes, products of 9-hydroxybenzo(a)pyrene were the predominant binding species. In a system containing isolated rat hepatocytes, the total binding was much lower, and products of trans-7,8-dihydroxy-7, 8-dihydrobenzo(a)pyrene predominated. Both the total amounts and the ratios of the bound species were altered by the addition of various soluble nucleophiles to the incubation system. The binding of 9-hydroxybenzo(a)pyrene to both nuclear and purified DNA was decreased in the presence of "non-specific" protein in the incubate. A decrease in the binding of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to either purified or nuclear DNA was seen after the addition of active cytosol, but not with protein alone. Either denaturation of the cytosol, or depletion of glutathione by diethylmaleate treatment, partially negated this effect. We conclude that the binding of benzo(a)pyrene metabolites to DNA in the cell is decreased by soluble nucleophiles, and that this trapping of metabolites is selective. 9-Hydroxybenzo(a)pyrene metabolites are removed by non-specific protein binding, whereas removal of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene metabolites requires higher affinity binding or enzymatic conjugation.

  6. New 7,8-benzoflavanones as potent aromatase inhibitors: synthesis and biological evaluation.

    PubMed

    Yahiaoui, Samir; Fagnere, Catherine; Pouget, Christelle; Buxeraud, Jacques; Chulia, Albert-José

    2008-02-01

    Some natural compounds such as flavonoids are known to possess a moderate inhibitory activity against aromatase, this enzyme being an interesting target for hormone-dependent breast cancer treatment. It has been demonstrated that the modulation of flavonoid skeleton could increase anti-aromatase effect. Therefore, new 7,8-benzoflavanones were synthesized and tested for their activity toward aromatase inhibition. It was observed that the introduction of a benzo ring at position C-7 and C-8 on flavanone skeleton led to new potent aromatase inhibitors, the resulting 7,8-benzoflavanones being until nine times more potent than aminogluthetimide (the first aromatase inhibitor used clinically).

  7. Ecuador's Higher Education System in Times of Change

    ERIC Educational Resources Information Center

    Van Hoof, Hubert B.; Estrella, Mateo; Eljuri, Marie-Isabel; León, Leonardo Torres

    2013-01-01

    Ecuador's higher education system is undergoing dramatic changes. The National Constitution of 2008 and the Higher Education Law of 2010 have changed the way Ecuador's universities are funded, administered, and accredited. The importance of research was elevated and drastic changes were made to the academic qualifications and employment conditions…

  8. Gridded atmospheric emission inventory of 2,3,7,8-TCDD in China

    NASA Astrophysics Data System (ADS)

    Huang, Tao; Tian, Chongguo; Zhang, Kai; Gao, Hong; Li, Yi-Fan; Ma, Jianmin

    2015-05-01

    Establishment of the dioxins emission inventory has been considered as a crucial step toward risk assessment and elimination of dioxins contaminations. Based on a total dioxin emission inventory in China from different emission categories in 2004, this study created a gridded emission inventory of 2,3,7,8-TCDD, the most toxic congener in dioxins, in China in 2009 with a 1/4° longitude by 1/4° latitude resolution. It was estimated that annually total 371 ± 53 g (average ± standard deviation) of 2,3,7,8-TCDD was released into the atmosphere in 2009 over China, increasing approximately by 37% compared with its emission in 2004. Differing from most developed countries where municipal waste incinerations were regarded as a major atmospheric emission source, in China ferrous and non-ferrous metal production made the largest contribution to 2,3,7,8-TCDD air emission (138 ± 16 g), followed by waste incineration (109 ± 12 g), power and heating generation (62 ± 9 g), and production of mineral products (47 ± 8 g). The rest of sources contributed approximately 3% to the total 2,3,7,8-TCDD emission in 2009. Iron and steel industries are mainly located in Beijing-Tianjin-Hebei (BTH) and Yangtze River Delta (YRD) regions, whereas waste incinerators are mainly located in Pearl River Delta (PRD) region. Higher 2,3,7,8-TCDD emissions were found in these three regions. While the BTH, YRD, and PRD accounted for only about 4% of total land area of China, they contributed approximately 14%, 15%, and 5% to the total 2,3,7,8-TCDD emission in 2009 in China, respectively.

  9. Time Management and Academic Achievement of Higher Secondary Students

    ERIC Educational Resources Information Center

    Cyril, A. Vences

    2015-01-01

    The only thing, which can't be changed by man, is time. One cannot get back time lost or gone Nothing can be substituted for time. Time management is actually self management. The skills that people need to manage others are the same skills that are required to manage themselves. The purpose of the present study was to explore the relation between…

  10. Crystal structures of two novel borate compounds MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8}

    SciTech Connect

    Li, H.K.; Cai, G.M.; Fan, J.J.; Jin, Z.P.; Zhou, T.T.; Chen, X.L.

    2013-06-15

    Two novel borate compounds MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8}, have been synthesized via solid-state reactions, and their crystal structures have been solved and refined from powder X-ray diffraction data. The compound MgInBO{sub 4}, which was obtained at 1190 °C, belongs to the warwickite family. It crystallizes in the Pnma space group (no. 62) with a=9.5443(1) Å, b=3.2771(1) Å, c=9.5228(1) Å, and Z=4. The fundamental building units are liner –Mg(In)O{sub 6}–[In(Mg)]{sub 2}O{sub 10}–Mg(In)O{sub 6}– chains and isolated BO{sub 3} triangles. The low-temperature phase, MgIn{sub 7/8}B{sub 7/8}O{sub 29/8}, whose crystal structure is solved ab initio by the charge-flipping method with standard chemical formula MgInBO{sub 4}, was prepared at 1080 °C. It crystallizes in the P12{sub 1}/n1 space group (no. 14) with a=17.0976(1) Å, b=3.2504(1) Å, c=5.3387(1) Å, β=96.0829(3)°, and Z=4. The structure of MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} contains [In(2)/Mg(2)]{sub 2}O{sub 10} groups, –MgO{sub 6}–InO{sub 6}– infinite ribbons and isolated BO{sub 3} triangles. The experiments and the differential thermal analysis (DTA) show the decompositions of MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} happen at about 1220 °C and 1180 °C, respectively. The comparative crystal chemistry from MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} to MgInBO{sub 4} has been discussed. Infrared spectra and UV–vis diffuse reflectance spectra of MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} were measured. - Graphical abstract: The structural transformation from the monoclinic MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} (P12{sub 1}/n1) to the orthorhombic MgInBO{sub 4} (Pnma). - Highlights: • Two novel borate compounds MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} have been synthesized via solid-state reactions for the first time. • The crystal structures of MgInBO{sub 4} and MgIn{sub 7/8}B{sub 7/8}O{sub 29/8} have been solved and refined from powder X

  11. SORPTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN FROM WATER BY SURFACE SOILS

    EPA Science Inventory

    The sorption of l4C-labeled 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) from water by two uncontaminated surface soils from the Times Beach, MO, area was evalu- ated by using batch shake testing. Sorption isotherm plots for the soil with the lower fraction organic carbon (f,) wer...

  12. Health Risk Assessment Approach for 2,3,7,8 ...

    EPA Pesticide Factsheets

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects various organ systems and is probably carcinogenic as well. The report documents the methodologies utilized by the United States Environmental Protection Agency in its development of health risk assessment from exposure to TCDD. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects various organ systems and is probably carcinogenic as well.

  13. Current skin symptoms of Yusho patients exposed to high levels of 2,3,4,7,8-pentachlorinated dibenzofuran and polychlorinated biphenyls in 1968.

    PubMed

    Mitoma, Chikage; Mine, Yoshiko; Utani, Atsushi; Imafuku, Shinichi; Muto, Masahiko; Akimoto, Takamichi; Kanekura, Takuro; Furue, Masutaka; Uchi, Hiroshi

    2015-10-01

    Yusho was a mass food poisoning event due to the ingestion of rice oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. At its outbreak in 1968, Yusho patients suffered severe skin symptoms. Although the blood concentrations of PCBs and dioxins, especially highly toxic 2,3,4,7,8-pentachlorinated dibenzofuran (2,3,4,7,8-PeCDF) remain high in these patients, extensive analysis has not been performed on their current skin symptoms. We categorized and evaluated the specific skin symptoms in Yusho in 2012 by grading their severity using an arbitrary scoring system, and analyzed their correlations with the blood concentrations of 2,3,4,7,8-PeCDF and PCBs. A total of 352 Yusho patients underwent annual dermatological check-ups, in which five skin symptoms: black comedones, acneiform eruptions, scar formation, pigmentation and nail deformity, were evaluated for their distribution and severity. Approximately one-third of Yusho patients still presented with black comedones, acneiform eruptions and scar formation; the distributions of these symptoms were similar to those at the time of the Yusho outbreak. The mean blood concentrations of 2,3,4,7,8-PeCDF and total PCBs in Yusho patients were still higher than those in controls. The prevalence and severity of black comedones were correlated with age. Severity scores of black comedones and scar formation were positively correlated with 2,3,4,7,8-PeCDF blood level, and those of black comedones, scar formation, and pigmentation were positively correlated with total PCBs blood level. This study suggests that 2,3,4,7,8-PeCDF and PCBs remaining in Yusho patients still play crucial roles in the development of skin symptoms in Yusho.

  14. Characterization of a recombinant 7,8-linoleate diol synthase from Glomerella cingulate.

    PubMed

    Seo, Min-Ju; Shin, Kyung-Chul; An, Jung-Ung; Kang, Woo-Ri; Ko, Yoon-Joo; Oh, Deok-Kun

    2016-04-01

    A putative diol synthase from the fungus Glomerella cingulate was cloned and expressed in Escherichia coli. The putative diol synthase from G. cingulate was purified by His-Trap affinity chromatography with a specific activity of 0.87 U mg(-1), an eightfold purification, and a yield of 28%. One unit of activity was defined as the amount of enzyme required to produce 1 μmol of 7,8-dihydroxy-9,12(Z,Z)-octadecadienoic acid (7,8-DiHODE) per min. The purified enzyme was estimated as a 127-kDa tetramer with a molecular mass of 510 kDa by gel filtration chromatography. The enzyme converted linoleic acid to a product, identified as 7S,8S-DiHODE by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectroscopy. The specific activity and catalytic efficiency (k cat/K m) of 7,8-diol synthase from G. cingulate for the conversion of fatty acid to dihydroxy fatty acid followed the order linoleic acid > α-linolenic acid > oleic acid > palmitoleic acid, indicating that the enzyme is a 7,8-linoleate diol synthase (7,8-LDS). The activity of the enzyme for the conversion of 7,8-DiHODE from linoleic acid was maximal at pH 6.5, 40 °C, and 2.5% (v/v) dimethyl sulfoxide (DMSO). Under these conditions, 7,8-LDS from G. cingulate converted 1.0 mM linoleic acid to 0.62 mM 7,8-DiHODE for 30 min, with a conversion yield of 62% (mol/mol), via 8-hydroperoxy-9,12(Z,Z)-octadecadienoic acid (8-HPODE) as an intermediate. The accumulation of 8-HPODE was due to a higher 8-dioxygenase activity in the N-terminal domain than hydroperoxide isomerase activity in the C-terminal domain.

  15. Restyling the Humanities Curriculum of Higher Education for Posthuman Times

    ERIC Educational Resources Information Center

    Siddiqui, Jamila R.

    2016-01-01

    The future viability of the humanities in higher education has been broadly debated. Yet, most of these debates are missing an important consideration. The humanities' object of study is the human, an object that some would argue has been replaced in our onto-epistemological systems by the posthuman. In her 2013 book, "The Posthuman,"…

  16. Rebooting Irish Higher Education: Policy Challenges for Challenging Times

    ERIC Educational Resources Information Center

    Hazelkorn, Ellen

    2014-01-01

    The 2008 global financial crisis cast a long shadow over Ireland's higher education and research system. The IMF said Ireland experienced an "unprecedented economic correction", while Ireland's National Economic and Social Development Office said Ireland was beset by five different crises: a banking crisis, a fiscal crisis, an economic…

  17. Higher Education in Times of Financial Distress: The Minnesota Experience

    ERIC Educational Resources Information Center

    Severns, Roger

    2012-01-01

    Like many states, Minnesota has incurred large budget deficits during the past two years. Those deficits have, in turn, led to changes in a number of areas of state government, particularly higher education. Faculty have incurred pay freezes and layoffs, programs have closed, and tuition increased. Campuses within the MnSCU system have been…

  18. Time Management in Higher Education Administration: A Case Study.

    ERIC Educational Resources Information Center

    Lewis, Darrell R.; Dahl, Tor

    How do departmental chairpersons and deans in a major university setting manage their time? What are the major administrative activities and functions associated with such responsibilities? What relationships do these have with an ability to delegate, to control one's time for planning and self-initiated activities, or personal sense of…

  19. Purification and properties of 7, 8-diaminopelargonic acid aminotransferase.

    PubMed

    Stoner, G L; Eisenberg, M A

    1975-06-10

    The enzyme 7, 8-diaminopelargonic acid aminotransferase utilizes S-adenosyl-L-methionine to transaminate the biotin precurson 7-keto-8-aminopelargonic acid and form the next intermediate in the pathway, 7, 8-diaminopelargonic acid. The enzyme has been purified nearly 1000-fold from an extract of a regulatory mutant of Escherichia coli which is derepressed for the enzymes of the biotin operon. The extract was treated with protamine sulfate, ammonium sulfate, and subjected to acid and heat treatments. Subsequently, the enzyme was chromatographed on columns of DEAE-cellulose, phosphocellulose, hydroxylapatite, and two Sephadex G-100. The resulting purified preparation was judged 86% homogeneous by the scanning of of a stained disc gel. The enzymatic activity was associated with the major band in gels run at two different gel concentrations and two different pH values. The cofactor, pyridoxal phosphate, can be resolved from the enzyme in the presence of phosphate buffer after incubation with the amino donor, S-adenosyl-L-methionine. A molecular weight estimation of 94,000 plus or minus 10, 000 has been obtained by gel filtration and sucrose gradient sedimentation studies. Gel electrophoresis in the presence of sodium dodecyl sulfate, shows a single subunit with a molecular weight of 47, 000 plus or minus 3, 000 indicating a dimeric enzyme. A neutral compound was detected in the acidified reaction mixture which was derived from the methionine moiety of S-adenosyl-L-methionine and was present in amounts equivalent to the 7, 8-diaminopelargonic acid produced in the reaction mixture. It is suggested that the keto product of the reaction, i.e. S-adenosyl-2-oxo-4-methylthiobutyric acid, may decompose nonenzymatically under the conditions of the reaction to form 5'-methylthioadenosine and the neutral compound, 2-oxo-3-butenoic acid.

  20. Time Management in Higher Education Administration: A Case Study

    ERIC Educational Resources Information Center

    Lewis, Darrell R.; Dahl, Tor

    1976-01-01

    Drawing on data from a staff development project for administrators in a college at a major American university, it was determined that there is considerable commonality across individuals and that it is possible to deal with such issues as time management, job stress, and enjoyment on an organizational level. (Editor/JT)

  1. Metabolism and distribution of benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) in human lung cells by liquid chromatography tandem mass spectrometry: detection of an adenine B[a]P-7,8-dione adduct.

    PubMed

    Huang, Meng; Liu, Xiaojing; Basu, Sankha S; Zhang, Li; Kushman, Mary E; Harvey, Ronald G; Blair, Ian A; Penning, Trevor M

    2012-05-21

    Benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) is produced in human lung cells by the oxidation of (±)-B[a]P-7,8-trans-dihydrodiol, which is catalyzed by aldo-keto reductases (AKRs). However, information relevant to the cell-based metabolism of B[a]P-7,8-dione is lacking. We studied the metabolic fate of 2 μM 1,3-[(3)H(2)]-B[a]P-7,8-dione in human lung adenocarcinoma A549 cells, human bronchoalveolar H358 cells, and immortalized human bronchial epithelial HBEC-KT cells. In these three cell lines, 1,3-[(3)H(2)]-B[a]P-7,8-dione was rapidly consumed, and radioactivity was distributed between the organic and aqueous phase of ethyl acetate-extracted media, as well as in the cell lysate pellets. After acidification of the media, several metabolites of 1,3-[(3)H(2)]-B[a]P-7,8-dione were detected in the organic phase of the media by high performance liquid chromatography-ultraviolet-radioactivity monitoring (HPLC-UV-RAM). The structures of B[a]P-7,8-dione metabolites varied in the cell lines and were identified as B[a]P-7,8-dione conjugates with glutathione (GSH) and N-acetyl-l-cysteine (NAC), 8-O-monomethylated-catechol, catechol monosulfate, and monoglucuronide, and monohydroxylated-B[a]P-7,8-dione by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We also obtained evidence for the first time for the formation of an adenine adduct of B[a]P-7,8-dione. Among these metabolites, the identity of the GSH-B[a]P-7,8-dione and the NAC-B[a]P-7,8-dione was further validated by comparison to authentic synthesized standards. The pathways of B[a]P-7,8-dione metabolism in the three human lung cell lines are formation of GSH and NAC conjugates, reduction to the catechol followed by phase II conjugation reactions leading to its detoxification, monohydroxylation, as well as formation of the adenine adduct.

  2. Synthesis and Characterization of Mono-, Di-, and Tetranitrated 7,8-Disubstituted Glycolurils

    DTIC Science & Technology

    2014-02-01

    information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...dictates the degree of nitration with few, if any, unwanted side products. While many substitution patterns exist in the literature for 7,8... Cheetah 7.0 [7] . All of the compounds 8–13 are predicted to have performance values less than TNT with 15 and 16 approaching the performance of TNT

  3. Leeds Undergraduate Medical Education Conference, 7-8 July 1995.

    PubMed

    Wilson, S; Reece, A; Sykes, A; Noble, A

    1996-03-01

    The Leeds Undergraduate Medical Education Conference (LUMEC) was held on 7-8 July 1995. This conference, devoted entirely to undergraduate medical education, was unique in that it was organized entirely by four medical students. It attracted a wide and enthusiastic audience and excellent speakers. Professor Charles George (Chairman, Education Committee, General Medical Council) spoke about Tomorrow's Doctors, Dr Mark Bailey (Part-chairman, Medical Students' Committee of the British Medical Association) responded with 'Today's Students on Tomorrow's Doctors', and Dr Fleur Fisher (Ethics, Science and Information Division, British Medical Association) focused on the central place of ethics and communication skills in medicine. Professor Sam Leinster (Director of Medical Studies, Liverpool University) and Professor Tim de Dombal (Director, Clinical Information Science Unit, Leeds University) debated the need for new technology and radical change in the curriculum. Finally, Dr Stella Lowry (International Division, British Medical Association) considered the assessment of staff and Mrs Joy Crosby (Curriculum Facilitator, Dundee Medical School) discussed the assessment of students. Discussions focused on a variety of areas, including the need for change, the control of the money available for teaching and the problems of assessment.

  4. Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its Derivatives with TrkB and VEGFR2 Proteins

    PubMed Central

    Chitranshi, Nitin; Gupta, Vivek; Kumar, Sanjay; Graham, Stuart L.

    2015-01-01

    7,8-Dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue. PMID:26404256

  5. 2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity.

    PubMed

    Pelclová, Daniela; Prázny, Martin; Skrha, Jan; Fenclová, Zdenka; Kalousová, Marta; Urban, Pavel; Navrátil, Tomás; Senholdová, Zdenka; Smerhovsky, Zdenek

    2007-09-01

    Vascular function was examined in subjects with long-term high level of serum 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) during their follow-up visits. Their earlier mean peak TCDD level at the time of exposure in 1965-1968 was estimated in the range of 3300-74 000 pg/g lipids. Ten former pesticide production workers heavily exposed to TCDD (age 57 +/- 2 years, TCDD about 170 pg/g lipids) were examined in 2001. Extended group of 15 TCDD-exposed men (age 59 +/- 3 years, TCDD about 130 pg/g lipids) underwent the same examination in 2004. Findings were compared with a control group of 14 healthy men (age 54 +/- 2 years). Skin microvascular reactivity (MVR) was measured by laser Doppler perfusion monitoring in the forearm during post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH). Several parameters of MVR in men exposed to TCDD were significantly impaired, compared with the control group and further progression of the impairment of MVR has been observed between years 2001 and 2004. Serum concentration of E-selectin and inhibitor of tissue plasminogen activator 1 (PAI-1) was significantly higher in exposed subjects (56.0 +/- 18.4 ng/mL versus 40.0 +/- 12.0 ng/mL, P = 0.022 and 90.9 +/- 33.3 ng/mL versus 45.0 +/- 18.0, P = 0.002, respectively). In addition, PORH in the forearm was significantly negatively associated with SOD activity (r = -0.77, P = 0.009) as well as the velocity of perfusion increase during TH (r = -0.68, P = 0.03) and TH% (r = -0.78, P = 0.008). Our data document the presence of endothelial dysfunction in TCDD-exposed men.

  6. Installation of 2 7/8-in. coiled-tubing tailpipes in live gas wells

    SciTech Connect

    Campbell, J.A.; Bayes, K.P.

    1994-05-01

    This paper describes a technique for installing 2 7/8-in. coiled tubing as tailpipe extensions below existing production packers in live gas wells. It also covers the use of coiled tubing as a way to complete wells. Large savings in rig time and deferred production have been realized with this technique. Fluid losses to the formation do not occur, and no expensive rig time is needed to kill or clean up the wells, as required for conventional workovers below existing production packers. This technique is particularly applicable in depleted reservoirs that could be impaired by traditional workover methods.

  7. Agora VII: Working Time, Training Time (Thessaloniki, Greece, October 7-8, 1999). CEDEFOP Panorama Series.

    ERIC Educational Resources Information Center

    Guggenheim, Eric Fries, Ed.

    This document contains the agenda and papers on work and training presented at the Agora VII meeting in Thessaloniki, Greece in October, 1999. The Foreword describes each session with a list of the topics and papers, along with a brief introduction to the topics. The three sessions are: Work and Training in Society in the 21st Century; Working…

  8. 36 CFR 7.8 - Sequoia and Kings Canyon National Parks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... National Parks. 7.8 Section 7.8 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.8 Sequoia and Kings Canyon National Parks. (a) Dogs and cats. Dogs and cats are prohibited on any park land or trail except within...

  9. 36 CFR 7.8 - Sequoia and Kings Canyon National Parks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... National Parks. 7.8 Section 7.8 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.8 Sequoia and Kings Canyon National Parks. (a) Dogs and cats. Dogs and cats are prohibited on any park land or trail except within...

  10. 36 CFR 7.8 - Sequoia and Kings Canyon National Parks.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... National Parks. 7.8 Section 7.8 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.8 Sequoia and Kings Canyon National Parks. (a) Dogs and cats. Dogs and cats are prohibited on any park land or trail except within...

  11. State Spending on Higher Education: Testing the Balance Wheel over Time

    ERIC Educational Resources Information Center

    Delaney, Jennifer A.; Doyle, William R.

    2011-01-01

    This article considers the role of higher education in state budgets. It empirically models and tests the balance wheel hypothesis in a robust framework. The balance wheel model posits that in good economic times, higher education is an attractive area for states to fund and tends to be funded at a higher rate than other state budget categories.…

  12. Part-Time Higher Education in English Colleges: Adult Identities in Diminishing Spaces

    ERIC Educational Resources Information Center

    Esmond, Bill

    2015-01-01

    Adult participation in higher education has frequently entailed mature students studying part time in lower-ranked institutions. In England, higher education policies have increasingly emphasised higher education provision in vocational further education colleges, settings which have extensive adult traditions but which mainly teach…

  13. Changing Times of Feminism and Higher Education: From Community to Employability

    ERIC Educational Resources Information Center

    Moss, Dorothy; Richter, Ingrid

    2011-01-01

    This article discusses the creation of space and time for feminist approaches in higher education in the context of shifting community and employment relations and the restructuring of higher education space-time. It draws on the reflections of three feminist academics concerning aspects of their work biographies in two very different higher…

  14. Time as the Fourth Dimension in the Globalization of Higher Education

    ERIC Educational Resources Information Center

    Walker, Judith

    2009-01-01

    This paper calls for an analysis of time to be integrated into the theories on the globalization of higher education. Specifically, the author argues that academic capitalism, fuelled by globalization, has led to changes in the university visible in time/space compression, time acceleration, the reification of time and our internalization of the…

  15. SORPTION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TO SOILS FROM WATER/METHANOL MIXTURES

    EPA Science Inventory

    Sorption of 14C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to soils from water/methanol mixtures has been evaluated by batch shake testing. Uncontaminated soils from Times Beach, MO, were used in these experiments and ranged in fraction organic carbon (U...

  16. Time-delay at higher genus in high-energy open string scattering*

    NASA Astrophysics Data System (ADS)

    Kuroki, T.; Rey, S.-J.

    2001-02-01

    We explore some aspects of causal time-delay in open string scattering studied recently by Seiberg, Susskind and Toumbas. By examining high-energy scattering amplitudes at higher order in perturbation theory, we argue that causal time-delay at /Gth order is /1/(G+1) times smaller than the time-delay at tree level. We propose a space-time interpretation of the result by utilizing the picture of the high-energy open string scattering put forward by Gross and Mañes. We argue that the phenomenon of reduced time-delay is attributed to the universal feature of the space-time string trajectory in high-energy scattering that string shape at higher order remains the same as that at tree level but overall scale is reduced. We also discuss implications to the space-time uncertainty principle and make brief comments on causal time-delay behavior in space/time noncommutative field theory.

  17. Seismotectonics and seismogenesis of Mw7.8 Gorkha earthquake and its aftershocks

    NASA Astrophysics Data System (ADS)

    Arora, B. R.; Bansal, B. K.; Prajapati, Sanjay K.; Sutar, Anup K.; Nayak, Shailesh

    2017-01-01

    The April 25, 2015, Mw7.8 Gorkha earthquake in central Nepal was followed by intense aftershock activity, including Mw6.7 shock on April 26, 2015 and Mw7.3 shock on May 12, 2015. Synthesis of the focal mechanisms, space-time distribution of seismic activity in relation to previously imaged crustal velocity and resistivity structures reveals focusing of the Mw7.8 Gorkha earthquake near the upper surface of the thin fluid-filled low velocity and high conducting layer immediately above the plane of the detachment. On the geophysical sections, the detachment is identified as a sharp positive velocity interface. Modulation of frictional coupling and mechanical weakening by high-pore pressure fluids counteract the arc-normal stresses creating conditions for failure and nucleation of the Gorkha earthquakes on a plane sub-parallel with the detachment. Spatio-temporal patterns in aftershock activity indicate rapid alteration of main shock-induced stress fields, triggering a strong aftershock of Mw6.7. Large stress drop and increased energy released by the Mw6.7 event facilitates upward injection of high pore-pressure fluid fluxes into the hidden out-of-sequence thrust. It is suggested that decrease in shear strength along the hidden thrust plane due to the diffusion of high pore pressure fluids created conditions favourable to trigger Mw7.3 aftershock.

  18. Pulse transmission receiver with higher-order time derivative pulse correlator

    DOEpatents

    Dress, Jr., William B.; Smith, Stephen F.

    2003-09-16

    Systems and methods for pulse-transmission low-power communication modes are disclosed. A pulse transmission receiver includes: a higher-order time derivative pulse correlator; a demodulation decoder coupled to the higher-order time derivative pulse correlator; a clock coupled to the demodulation decoder; and a pseudorandom polynomial generator coupled to both the higher-order time derivative pulse correlator and the clock. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.

  19. Part-Time Faculty in Colleges and Universities. 1981 Current Issues in Higher Education, No. 4.

    ERIC Educational Resources Information Center

    American Association for Higher Education, Washington, DC.

    Characteristics of part-time faculty, the legal position of part-time faculty, faculty development for part-timers, and other concerns are addressed in four papers. Thomas A. Emmet mentions the activities of some higher education associations with regard to the part-time employment issue and identifies 10 considerations for practices for these…

  20. Higher Education Students in Part-Time Work in a Chinese City

    ERIC Educational Resources Information Center

    Morrison, Keith

    2009-01-01

    This article discusses students taking part-time work whilst studying higher education (HE). It suggests that cross-national trends can be observed in the purposes, types, benefits, negative aspects and outcomes of part-time work by HE students. The paper reviews literature on HE students working part-time in the UK and the US, and UNESCO studies…

  1. Thermal management for heavy vehicles (Class 7-8 trucks)

    SciTech Connect

    Wambsganss, M.W.

    2000-04-03

    Thermal management is a crosscutting technology that has an important effect on fuel economy and emissions, as well as on reliability and safety, of heavy-duty trucks. Trends toward higher-horsepower engines, along with new technologies for reducing emissions, are substantially increasing heat-rejection requirements. For example, exhaust gas recirculation (EGR), which is probably the most popular near-term strategy for reducing NO{sub x} emissions, is expected to add 20 to 50% to coolant heat-rejection requirements. There is also a need to package more cooling in a smaller space without increasing costs. These new demands have created a need for new and innovative technologies and concepts that will require research and development, which, due to its long-term and high-risk nature, would benefit from government funding. This document outlines a research program that was recommended by representatives of truck manufacturers, engine manufacturers, equipment suppliers, universities, and national laboratories. Their input was obtained through personal interviews and a plenary workshop that was sponsored by the DOE Office of Heavy Vehicle Technologies and held at Argonne National Laboratory on October 19--20, 1999. Major research areas that received a strong endorsement by industry and that are appropriate for government funding were identified and included in the following six tasks: (1) Program management/coordination and benefits/cost analyses; (2) Advanced-concept development; (3) Advanced heat exchangers and heat-transfer fluids; (4) Simulation-code development; (5) Sensors and control components development; and (6) Concept/demonstration truck sponsorship.

  2. Risk of Birth Defects 20 Times Higher for Zika Moms: CDC

    MedlinePlus

    ... Birth Defects 20 Times Higher for Zika Moms: CDC Finding highlights importance of preventing infection during pregnancy, ... officer in the birth defects branch of the CDC, noted that in this report the investigators only ...

  3. Matrix metalloproteinases -1, -2, -3, -7, -8, -12, and -13 in gingival crevicular fluid during orthodontic tooth movement: a longitudinal randomized split-mouth study.

    PubMed

    Canavarro, Cristiane; Teles, Ricardo Palmier; Capelli Júnior, Jonas

    2013-10-01

    This randomized split-mouth study aimed to examine the levels of matrix metalloproteinases (MMPs) -1, -2, -3, -7, -8, -12, and -13 in the gingival crevicular fluid (GCF) at different time points during orthodontic tooth movement. A total of 16 healthy orthodontic subjects (7 females, 9 males; mean age, 17.7 years) who needed their first upper premolars extracted were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force and was considered to be the test side. The contralateral canine, which was not subjected to any force but was included in the orthodontic appliance, was used as a control side. GCF sampling was performed at both the mesial (tension) and distal (pressure) test and control sites at baseline, immediately before applying the orthodontic appliance, and after 1 and 24 hours and 7, 14, and 21 days. A multiplexed bead immunoassay was used to analyse the GCF samples. The mean levels of the MMP-1, -2, -3, -7, -8, -12, and -13 were not significantly different between the test and control groups in each time showed. The comparisons between the tension and pressure sites were also not significantly different at each individual time. A few variations focused on MMP-1 and -3, but the expression of MMP-8 was higher than that of the other MMPs. MMPs are released in sufficient quantities such that tooth movement occurs but with no significant increase in GCF levels.

  4. Time Work by Overworked Professionals: Strategies in Response to the Stress of Higher Status

    PubMed Central

    Moen, Phyllis; Lam, Jack; Ammons, Samantha; Kelly, Erin L.

    2013-01-01

    How are professionals responding to the time strains brought on by the stress of their higher status jobs? Qualitative data from professionals reveal (a) general acceptance of the emerging temporal organization of professional work, including rising time demands and blurred boundaries around work/ nonwork times and places, and (b) time work as strategic responses to work intensification, overloads, and boundarylessness. We detected four time-work strategies: prioritizing time, scaling back obligations, blocking out time, and time shifting of obligations. These strategies are often more work-friendly than family-friendly, but “blocking out time” and “time shifting” suggest promising avenues for work-time policy and practice. PMID:24039337

  5. Part-time Faculty Job Satisfaction in Higher Education: A Literature Review

    ERIC Educational Resources Information Center

    Howell, Scott L.; Hoyt, Jeff

    2007-01-01

    The purpose of this literature review was to inform researchers of those predictive factors of job satisfaction previously identified for part-time faculty in higher education. They used the information gathered to help develop a survey instrument that was administered to 700 part-time faculty at their own institution. The results of the study,…

  6. Preparation and Support for Part-Time Teachers in Higher Education: Case Studies of Departmental Practice.

    ERIC Educational Resources Information Center

    Forster, Fred, Comp.; Thompson, Sheila, Comp.

    This publication presents 14 departmental case studies of the preparation and support provided to part-time teachers in Scottish institutions of higher education. The case studies are grouped in four sections according to the category of part-time staff involved: practicing professionals (professional teaching assistants, lawyers, artists, and…

  7. The Supply of Part-Time Higher Education in the UK. Research Report

    ERIC Educational Resources Information Center

    Callender, Claire; Birkbeck, Anne Jamieson; Mason, Geoff

    2010-01-01

    This report explores the supply of part-time higher education in the UK, with particular consideration to the study of part-time undergraduate provision in England. It is the final publication in the series of reports on individual student markets that were commissioned by Universities UK following the publication of the reports on the Future size…

  8. 7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice

    PubMed Central

    Tan, Yang; Nie, Shuke; Zhu, Wende; Liu, Fang; Guo, Hailong; Chu, Jiewen; Cao, Xue B.; Jiang, Xingjun; Zhang, Yunjian; Li, Yuzhen

    2016-01-01

    7,8-Dihydroxyflavone (7,8-DHF), a tyrosine kinase B agonist that mimics the neuroprotective properties of brain-derived neurotrophic factor, which can not efficiently deliver into the brain, has been reported to be useful in ameliorating cognitive impairment in many diseases. Researches have indicated that apolipoprotein E-knockout (ApoE-KO) mouse was associated with cognitive alteration via various mechanisms. Our present study investigated the possible mechanisms of cognitive impairment of ApoE-KO mouse fed with western type diet and the protective effects of 7,8-DHF in improving spatial learning and memory in ApoE-KO mouse. Five-weeks-old ApoE-KO mice and C57BL/6 mice were chronically treated with 7,8-DHF (with a dosage of 5 mg/kg) or vehicles orally for 25 weeks, and then subjected to Morris water maze at the age of 30 weeks to evaluate the cognitive performances. Afterward, histology analysis and western blotting were performed. Spatial learning and memory deficits were observed in ApoE-KO mice, which were consistent with higher expression of active-asparaginyl endopeptidase (active-AEP) as well as AEP-derived truncated tau N368 compared with normal group. In addition to that, long-term treatment of 7,8-DHF dramatically ameliorated cognitive decline in ApoE-KO mice, accompanied by the activation in phosphorylated protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway and down-regulated expression of tau S396 and PHF-tau (phosphorylated tau at ser396 and ser404 epitope). These findings suggested that cognitive impairment of ApoE-KO mouse might associate with tau pathology and 7,8-DHF could activate AKT and then phosphorylate its downstream molecule to inhibit expression of abnormal tau, meanwhile, 7,8-DHF could reduce the expression of active-AEP and then inhibit production of truncated tau N368. PMID:27965573

  9. Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9

    PubMed Central

    Kandimalla, Ekambar R.; Bhagat, Lakshmi; Wang, Daqing; Yu, Dong; Sullivan, Tim; La Monica, Nicola; Agrawal, Sudhir

    2013-01-01

    Oligonucleotides containing an immune-stimulatory motif and an immune-regulatory motif act as antagonists of Toll-like receptor (TLR)7 and TLR9. In the present study, we designed and synthesized oligonucleotide-based antagonists of TLR7, 8 and 9 containing a 7-deaza-dG or arabino-G modification in the immune-stimulatory motif and 2′-O-methylribonucleotides as the immune-regulatory motif. We evaluated the biological properties of these novel synthetic oligoribonucleotides as antagonists of TLRs 7, 8 and 9 in murine and human cell-based assays and in vivo in mice and non-human primates. In HEK293, mouse and human cell-based assays, the antagonist compounds inhibited signaling pathways and production of a broad range of cytokines, including tumour necrosis factor alpha (TNF-α), interleukin (IL)-12, IL-6, interferon (IFN)-α, IL-1β and interferon gamma-induced protein (IP)-10, mediated by TLR7, 8 and 9. In vivo in mice, the antagonist compounds inhibited TLR7- and TLR9-mediated cytokine induction in a dose- and time-dependent fashion. Peripheral blood mononuclear cells (PBMCs) obtained from antagonist compound-treated monkeys secreted lower levels of TLR7-, 8- and 9-mediated cytokines than did PBMCs taken before antagonist administration. The antagonist compounds described herein provide novel agents for the potential treatment of autoimmune and inflammatory diseases. PMID:23396449

  10. Spectrofluorimetric study of the charge-transfer complexation of certain fluoroquinolones with 7,7,8,8-tetracyanoquinodimethane

    NASA Astrophysics Data System (ADS)

    Du, Li Ming; Yao, Hai Yan; Fu, Mi

    2005-01-01

    Simple, rapid and sensitive spectrofluorimetric methods are described, for the first time, for the determination of ciprofloxacin (CIP), norfloxacin (NOR), pefloxacin (PEF) and fleroxacin (FLE). The methods are based on the charge-transfer (CT) reaction of these drugs as n-electron donors with 7,7,8,8-tetracyanoquinodimethane (TCNQ) as π-electron acceptor. TCNQ was found to react with these drugs to produce intensely transfer reaction complexes and the fluorescence intensity of the complexes was enhanced in 21-35 fold higher than that of the studied fluoroquinolones itself. The formation of such complexes was also confirmed by both infrared and ultraviolet-visible measurements. The different experimental parameters that affect the fluorescence intensity were carefully studied. At the optimum reaction conditions, the drug-TCNQ complexes showed excitation maxima ranging from 277 to 284 nm and emission maxima ranging from 451 to 458 nm. Rectilinear calibration graphs were obtained in the concentration range of 0.03-0.9, 0.04-1.2, 0.04-1.3 and 0.08-2.4 μg ml -1 for CIP, NOR, PEF and FLE, respectively. The developed methods were applied successfully for the determination of the studied drugs in their pharmaceutical dosage forms with a good precision and accuracy compared to official and reported methods as revealed by t- and F-tests.

  11. Bioavailability of 2,3,7,8-TCDD, 2,3,7,8-TCDF and PCBs to marine benthos from passaic river sediments

    SciTech Connect

    Rubinstein, N.I.; Pruell, R.J.; Taplin, B.K.; LiVolsi, J.A.; Norwood, C.B.

    1990-01-01

    The bioaccumulation and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran and polychlorinated biphenyls by marine benthos exposed to environmentally contaminated sediment were measured in a laboratory study. Sandworms (Nereis virens), clams (Macoma nasuta) and shrimp (Palaemonetes pugio) were exposed to sediment from the Passaic River, New Jersey for up to 180 days. Worms accumulated the highest concentrations of these compounds. Uptake and depuration rates were slowest in the worms and most rapid in the clams.

  12. Higher order finite-time consensus protocol for heterogeneous multi-agent systems

    NASA Astrophysics Data System (ADS)

    Zhou, Yingjiang; Yu, Xinghuo; Sun, Changyin; Yu, Wenwu

    2015-02-01

    This paper studies the higher order finite-time consensus protocol for heterogeneous multi-agent systems (HMASs). By adding a power integrator method and using heterogeneous domination method, two kinds of consensus protocols are proposed with state feedback and output feedback, respectively. First, for the leaderless and leader-follower HMASs, the continuous finite-time consensus protocols are proposed. Then, by designing a finite-time observer, the output-feedback finite-time consensus protocol is developed. Finally, simulations are performed to illustrate the effectiveness of the theoretical results.

  13. A convenient synthesis of delta(7,8)-morphinan-6-one and its direct oxidation to 14-hydroxy-delta(7,8)-morphinan-6-one.

    PubMed

    Passarella, Daniele; Consonni, Alessandra; Giardini, Alessandra; Lesma, Giordano; Silvani, Alessandra

    2002-08-05

    Synthesis of Delta(7,8)-morphinan-6-one by Grewe cyclization and bromoketalization reaction as crucial steps is described. Introduction of a hydroxyl group at 14-position is demonstrated by direct oxidation with MnO(2) in the presence of silica gel.

  14. Finite time control for MIMO nonlinear system based on higher-order sliding mode.

    PubMed

    Liu, Xiangjie; Han, Yaozhen

    2014-11-01

    Considering a class of MIMO uncertain nonlinear system, a novel finite time stable control algorithm is proposed based on higher-order sliding mode concept. The higher-order sliding mode control problem of MIMO nonlinear system is firstly transformed into finite time stability problem of multivariable system. Then continuous control law, which can guarantee finite time stabilization of nominal integral chain system, is employed. The second-order sliding mode is used to overcome the system uncertainties. High frequency chattering phenomenon of sliding mode is greatly weakened, and the arbitrarily fast convergence is reached. The finite time stability is proved based on the quadratic form Lyapunov function. Examples concerning the triple integral chain system with uncertainty and the hovercraft trajectory tracking are simulated respectively to verify the effectiveness and the robustness of the proposed algorithm.

  15. Higher-Order, Space-Time Adaptive Finite Volume Methods: Algorithms, Analysis and Applications

    SciTech Connect

    Minion, Michael

    2014-04-29

    The four main goals outlined in the proposal for this project were: 1. Investigate the use of higher-order (in space and time) finite-volume methods for fluid flow problems. 2. Explore the embedding of iterative temporal methods within traditional block-structured AMR algorithms. 3. Develop parallel in time methods for ODEs and PDEs. 4. Work collaboratively with the Center for Computational Sciences and Engineering (CCSE) at Lawrence Berkeley National Lab towards incorporating new algorithms within existing DOE application codes.

  16. An efficient higher-order PML in WLP-FDTD method for time reversed wave simulation

    NASA Astrophysics Data System (ADS)

    Wei, Xiao-Kun; Shao, Wei; Ou, Haiyan; Wang, Bing-Zhong

    2016-09-01

    Derived from a stretched coordinate formulation, a higher-order complex frequency shifted (CFS) perfectly matched layer (PML) is proposed for the unconditionally stable finite-difference time-domain (FDTD) method based on weighted Laguerre polynomials (WLPs). The higher-order PML is implemented with an auxiliary differential equation (ADE) approach. In order to further improve absorbing performance, the parameter values of stretching functions in the higher-order PML are optimized by the multi-objective genetic algorithm (MOGA). The optimal solutions can be chosen from the Pareto front for trading-off between two independent objectives. It is shown in a numerical test that the higher-order PML is efficient in terms of attenuating propagating waves and reducing late time reflections. Moreover, the higher-order PML can be placed very close to the wall when analyzing the channel characteristics of time reversal (TR) waves in a multipath indoor environment. Numerical examples of TR wave propagation demonstrate the availability of the proposed method.

  17. Institutional View of Part-Time Faculty Management in Higher Education Institutes in China

    ERIC Educational Resources Information Center

    Li, Zhifeng; Jiang, Xiulan; Li, Hongbo

    2007-01-01

    Part-time faculty has become an important labor force in Chinese colleges and universities. The number of them has risen rapidly and its structure varies in different types of higher education institutes (HEIs), which results from integration of the social motivation and the inner motivation of schools' reform. From the institutional point of…

  18. Curriculum Characteristics of Time-Compressed Course in a U.S. Higher Education Institution

    ERIC Educational Resources Information Center

    Hyun, Eunsook; Kretovics, Mark; Crowe, Alicia

    2006-01-01

    The study explored characteristics of the curriculum practice of higher education faculty in the context of time-compressed (e.g., 5-6 weeks) courses as compared with regular term (15-16 weeks) courses. The researchers used open-ended questions on a web-based survey at a large doctoral-extensive university in a Midwestern state in the United…

  19. "Times Higher Education" 100 under 50 Ranking: Old Wine in a New Bottle?

    ERIC Educational Resources Information Center

    Soh, Kaycheng

    2013-01-01

    "Times Higher Education" 100 under 50 ranking is a new twist to the university ranking. It focuses on universities that have a history of 50 years or less with the purpose of offsetting the advantage of prestige of the older ones. This article re-analysed the data publicly available and looked into relevant conceptual and statistical issues. The…

  20. What Determines Employment of Part-Time Faculty in Higher Education Institutions?

    ERIC Educational Resources Information Center

    Liu, Xiangmin; Zhang, Liang

    2007-01-01

    This study uses a cross-section national sample of four-year colleges and universities in the United States to examine the variation of part-time faculty employment. Results of this study suggest that higher educational institutions actively design and adopt contingent work arrangements to save on labor costs and to manage their resource…

  1. Analyzing the Anglo-American Hegemony in the "Times Higher Education" Rankings

    ERIC Educational Resources Information Center

    Kaba, Amadu Jacky

    2012-01-01

    This study analyzes the 2009 "Times Higher Education"-QS top 200 universities in the world. Based on this analysis the study claims that the THS reflects the phenomenon of Anglo American hegemony. The United States with 54 universities and the United Kingdom with 29 dominated the THS. In addition, six out of every ten universities on the…

  2. Inequalities in Entry to Higher Education: A Comparison over Time between Scotland and England and Wales

    ERIC Educational Resources Information Center

    Iannelli, Cristina

    2007-01-01

    This paper uses data from the Scottish School Leavers Surveys and the England and Wales Youth Cohort Study to analyse changes over time in gender and social class inequalities in the opportunities of young people to participate in higher education (HE) in Scotland, England and Wales. The results show that in Great Britain, in the period from the…

  3. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone

    PubMed Central

    Jang, Sung-Wuk; Liu, Xia; Yepes, Manuel; Shepherd, Kennie R.; Miller, Gary W.; Liu, Yang; Wilson, W. David; Xiao, Ge; Blanchi, Bruno; Sun, Yi E.; Ye, Keqiang

    2010-01-01

    Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases. PMID:20133810

  4. Flavonoid derivative 7,8-DHF attenuates TBI pathology via TrkB activation.

    PubMed

    Agrawal, Rahul; Noble, Emily; Tyagi, Ethika; Zhuang, Yumei; Ying, Zhe; Gomez-Pinilla, Fernando

    2015-05-01

    Traumatic brain injury (TBI) is followed by a state of metabolic dysfunction, affecting the ability of neurons to use energy and support brain plasticity; there is no effective therapy to counteract the TBI pathology. Brain-derived neurotrophic factor (BDNF) has an exceptional capacity to support metabolism and plasticity, which highly contrasts with its poor pharmacological profile. We evaluated the action of a flavonoid derivative 7,8-dihydroxyflavone (7,8-DHF), a BDNF receptor (TrkB) agonist with the pharmacological profile congruent for potential human therapies. Treatment with 7,8-DHF (5mg/kg, ip, daily for 7 days) was effective to ameliorate the effects of TBI on plasticity markers (CREB phosphorylation, GAP-43 and syntaxin-3 levels) and memory function in Barnes maze test. Treatment with 7,8-DHF restored the decrease in protein and phenotypic expression of TrkB phosphorylation after TBI. In turn, intrahippocampal injections of K252a, a TrkB antagonist, counteracted the 7,8-DHF induced TrkB signaling activation and memory improvement in TBI, suggesting the pivotal role of TrkB signaling in cognitive performance after brain injury. A potential action of 7,8-DHF on cell energy homeostasis was corroborated by the normalization in levels of PGC-1α, TFAM, COII, AMPK and SIRT1 in animals subjected to TBI. Results suggest a potential mechanism by which 7,8-DHF counteracts TBI pathology via activation of the TrkB receptor and engaging the interplay between cell energy management and synaptic plasticity. Since metabolic dysfunction is an important risk factor for the development of neurological and psychiatric disorders, these results set a precedent for the therapeutic use of 7,8-DHF in a larger context.

  5. Flavonoid derivative 7,8-DHF attenuates TBI pathology via TrkB activation

    PubMed Central

    Agrawal, Rahul; Noble, Emily; Tyagi, Ethika; Zhuang, Yumei; Ying, Zhe; Gomez-Pinilla, Fernando

    2015-01-01

    Traumatic brain injury (TBI) is followed by a state of metabolic dysfunction, affecting the ability of neurons to use energy and support brain plasticity; there is no effective therapy to counteract the TBI pathology. Brain-derived neurotrophic factor (BDNF) has an exceptional capacity to support metabolism and plasticity, which highly contrasts with its poor pharmacological profile. We evaluated the action of a flavonoid derivative 7,8-dihydroxyflavone (7,8-DHF), a BDNF receptor (TrkB) agonist with the pharmacological profile congruent for potential human therapies. Treatment with 7,8-DHF (5 mg/kg, ip, daily for 7 days) was effective to ameliorate the effects of TBI on plasticity markers (CREB phosphorylation, GAP-43 and syntaxin-3 levels) and memory function in Barnes maze test. Treatment with 7,8-DHF restored the decrease in protein and phenotypic expression of TrkB phosphorylation after TBI. In turn, intrahippocampal injections of K252a, a TrkB antagonist, counteracted the 7,8-DHF induced TrkB signaling activation and memory improvement in TBI, suggesting the pivotal role of TrkB signaling in cognitive performance after brain injury. A potential action of 7,8-DHF on cell energy homeostasis was corroborated by the normalization in levels of PGC-1α, TFAM, COII, AMPK and SIRT1 in animals subjected to TBI. Results suggest a potential mechanism by which 7,8-DHF counteracts TBI pathology via activation of the TrkB receptor and engaging the interplay between cell energy management and synaptic plasticity. Since metabolic dysfunction is an important risk factor for the development of neurological and psychiatric disorders, these results set a precedent for the therapeutic use of 7,8-DHF in a larger context. PMID:25661191

  6. Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures

    PubMed Central

    Eadon, George; Kaminsky, Laurence; Silkworth, Jay; Aldous, Kenneth; Hilker, David; O'Keefe, Patrick; Smith, Robert; Gierthy, John; Hawley, John; Kim, Nancy; DeCaprio, Anthony

    1986-01-01

    Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the “2,3,7,8-TCDD equivalent” concentration of a mixture in order to “predict” its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds. PMID:3830107

  7. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties.

    PubMed

    Finnilä, Mikko A J; Zioupos, Peter; Herlin, Maria; Miettinen, Hanna M; Simanainen, Ulla; Håkansson, Helen; Tuukkanen, Juha; Viluksela, Matti; Jämsä, Timo

    2010-04-19

    Dioxins are known to decrease bone strength, architecture and density. However, their detailed effects on bone material properties are unknown. Here we used nanoindentation methods to characterize the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on nanomechanical behaviour of bone matrix. Pregnant rats were treated with a single intragastric dose of TCDD (1 microg/kg) or vehicle on gestational day 11. Tibias of female offspring were sampled on postnatal day (PND) 35 or 70, scanned at mid-diaphysis with pQCT, and evaluated by three-point bending and nanoindentation. TCDD treatment decreased bone mineralization (p<0.05), tibial length (p<0.01), cross-sectional geometry (p<0.05) and bending strength (p<0.05). Controls showed normal maturation pattern between PND 35 and 70 with decreased plasticity by 5.3% and increased dynamic hardness, storage and complex moduli by 26%, 13% and 12% respectively (p<0.05), while similar maturation was not observed in TCDD-exposed pups. In conclusion, for the first time, we demonstrate retardation of bone matrix maturation process in TCDD-exposed animals. In addition, the study confirms that developmental TCDD exposure has adverse effects on bone size, strength and mineralization. The current results in conjunction with macromechanical behaviour suggest that reduced bone strength caused by TCDD is more associated with the mineralization and altered geometry of bones than with changes at the bone matrix level.

  8. Application of pharmacokinetic modelling for 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure assessment.

    PubMed

    Ruiz, P; Aylward, L L; Mumtaz, M

    2014-01-01

    Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs). The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD). Historically, DLCs have caused a variety of negative human health effects, but a disfiguring skin condition known as chloracne is the only health effect reported consistently. As part of translational research to make computerized models accessible to health risk assessors, the Concentration- and Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna simulation language. The US Agency for Toxic Substances and Disease Registry's computational toxicology laboratory used the recoded model to predict TCDD tissue concentrations at different exposure levels. The model simulations successfully reproduced the National Health and Nutrition Examination Survey (NHANES) 2001-2002 TCDD data in age groups from 6 to 60 years and older, as well as in other human datasets. The model also enabled the estimation of lipid-normalized serum TCDD concentrations in breastfed infants. The model performed best for low background exposures over time compared with a high acute poisoning case that could due to the large dose and associated liver toxicity. Hence, this model may be useful for interpreting human biomonitoring data as a part of an overall DLC risk assessment.

  9. Fingerprinting 2,3,7,8-tetrachlorodibenzodioxin contamination within the lower Passaic River.

    PubMed

    Quadrini, James D; Ku, Wen; Connolly, John P; Chiavelli, Deborah A; Israelsson, Peter H

    2015-07-01

    The lower Passaic River is an operable unit of the Diamond Alkali Superfund site at 80 and 120 Lister Avenue in Newark, New Jersey, USA. Between 1948 and 1969, the Diamond Shamrock Chemicals Company and its predecessors manufactured chemicals such as pesticides and phenoxy herbicides, including 2,4,5-trichlorophenol, which is a precursor to 2,4,5-trichlorophenoxyacetic acid, one of the primary components used to make the military defoliant Agent Orange. A by-product of this manufacturing process was 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD), and the site is considered the dominant source of 2,3,7,8-TCDD to the lower Passaic River and its environs. Several investigators have identified the ratio of 2,3,7,8-TCDD to total TCDD as a fingerprint for the site source. The present study presents data that establish polychlorinated dibenzodioxin/polychlorinated dibenzofuran (collectively, PCDD/F) congener and homolog fingerprints of soil and sump samples from the site. It then compares those fingerprints to the PCDD/F congener and homolog patterns in lower Passaic River sediments. The similarity of the patterns in lower Passaic River sediments to the site fingerprint indicates the site is the dominant source of the 2,3,7,8-TCDD in sediments within approximately the lower 14 miles of the lower Passaic River, excluding, for the purposes of the present discussion, Newark Bay. In addition, PCDD/F congener data indicate that the ratio of 1,3,7,8-TCDD to 2,3,7,8-TCDD is another marker of the site and corroborates the findings from the other fingerprints.

  10. Fingerprinting 2,3,7,8-tetrachlorodibenzodioxin contamination within the lower Passaic River

    PubMed Central

    Quadrini, James D; Ku, Wen; Connolly, John P; Chiavelli, Deborah A; Israelsson, Peter H

    2015-01-01

    The lower Passaic River is an operable unit of the Diamond Alkali Superfund site at 80 and 120 Lister Avenue in Newark, New Jersey, USA. Between 1948 and 1969, the Diamond Shamrock Chemicals Company and its predecessors manufactured chemicals such as pesticides and phenoxy herbicides, including 2,4,5-trichlorophenol, which is a precursor to 2,4,5-trichlorophenoxyacetic acid, one of the primary components used to make the military defoliant Agent Orange. A by-product of this manufacturing process was 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD), and the site is considered the dominant source of 2,3,7,8-TCDD to the lower Passaic River and its environs. Several investigators have identified the ratio of 2,3,7,8-TCDD to total TCDD as a fingerprint for the site source. The present study presents data that establish polychlorinated dibenzodioxin/polychlorinated dibenzofuran (collectively, PCDD/F) congener and homolog fingerprints of soil and sump samples from the site. It then compares those fingerprints to the PCDD/F congener and homolog patterns in lower Passaic River sediments. The similarity of the patterns in lower Passaic River sediments to the site fingerprint indicates the site is the dominant source of the 2,3,7,8-TCDD in sediments within approximately the lower 14 miles of the lower Passaic River, excluding, for the purposes of the present discussion, Newark Bay. In addition, PCDD/F congener data indicate that the ratio of 1,3,7,8-TCDD to 2,3,7,8-TCDD is another marker of the site and corroborates the findings from the other fingerprints. Environ Toxicol Chem 2015;34:1485–1498. © 2015 The Authors. Published by SETAC. PMID:25726763

  11. American Higher Education in 1975 and 1976: The Academy's Response to Continuing Kondratieff Recession as Reported in "The Times Higher Education Supplement" (London).

    ERIC Educational Resources Information Center

    Hawley, John B.; And Others

    Articles on American higher education that appeared in 1975 and 1976 in "The Times Higher Education Supplement" (London) are analyzed in connection with two statements about American society and its economy. These statements are Joseph A. Schumpeter's 1939 analysis of business cycles, and James B. Shuman's and Davis Rosenau's 1972…

  12. Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties

    SciTech Connect

    Shi, Genbin; Shaw, Gary; Liang, Yu-He; Subburaman, Priadarsini; Li, Yue; Wu, Yan; Yan, Honggao; Ji, Xinhua

    2012-07-11

    6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. The enzyme is essential for microorganisms, is absent from humans, and is not the target for any existing antibiotics. Therefore, HPPK is an attractive target for developing novel antimicrobial agents. Previously, we characterized the reaction trajectory of HPPK-catalyzed pyrophosphoryl transfer and synthesized a series of bisubstrate analog inhibitors of the enzyme by linking 6-hydroxymethylpterin to adenosine through 2, 3, or 4 phosphate groups. Here, we report a new generation of bisubstrate analog inhibitors. To improve protein binding and linker properties of such inhibitors, we have replaced the pterin moiety with 7,7-dimethyl-7,8-dihydropterin and the phosphate bridge with a piperidine linked thioether. We have synthesized the new inhibitors, measured their K{sub d} and IC{sub 50} values, determined their crystal structures in complex with HPPK, and established their structure-activity relationship. 6-Carboxylic acid ethyl ester-7,7-dimethyl-7,8-dihydropterin, a novel intermediate that we developed recently for easy derivatization at position 6 of 7,7-dimethyl-7,8-dihydropterin, offers a much high yield for the synthesis of bisubstrate analogs than that of previously established procedure.

  13. Calculating Higher-Order Moments of Phylogenetic Stochastic Mapping Summaries in Linear Time.

    PubMed

    Dhar, Amrit; Minin, Vladimir N

    2017-02-08

    Stochastic mapping is a simulation-based method for probabilistically mapping substitution histories onto phylogenies according to continuous-time Markov models of evolution. This technique can be used to infer properties of the evolutionary process on the phylogeny and, unlike parsimony-based mapping, conditions on the observed data to randomly draw substitution mappings that do not necessarily require the minimum number of events on a tree. Most stochastic mapping applications simulate substitution mappings only to estimate the mean and/or variance of two commonly used mapping summaries: the number of particular types of substitutions (labeled substitution counts) and the time spent in a particular group of states (labeled dwelling times) on the tree. Fast, simulation-free algorithms for calculating the mean of stochastic mapping summaries exist. Importantly, these algorithms scale linearly in the number of tips/leaves of the phylogenetic tree. However, to our knowledge, no such algorithm exists for calculating higher-order moments of stochastic mapping summaries. We present one such simulation-free dynamic programming algorithm that calculates prior and posterior mapping variances and scales linearly in the number of phylogeny tips. Our procedure suggests a general framework that can be used to efficiently compute higher-order moments of stochastic mapping summaries without simulations. We demonstrate the usefulness of our algorithm by extending previously developed statistical tests for rate variation across sites and for detecting evolutionarily conserved regions in genomic sequences.

  14. Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Fingerhut, M.A.; Halperin, W.E.; Marlow, D.A.; Piacitelli, L.A.; Honchar, P.A.; Sweeney, M.H.; Greife, A.L.; Dill, P.A.; Steenland, K.; Suruda, A.J. )

    1991-01-24

    In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer. We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD. Occupational exposure was documented by reviewing job descriptions and by measuring TCDD in serum from a sample of 253 workers. Causes of death were taken from death certificates. Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort. Mortality from soft-tissue sarcoma was increased, but not significantly (4 deaths; standardized mortality ratio (SMR), 338; 95 percent confidence interval, 92 to 865). In the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency, however, mortality was significantly increased for soft-tissue sarcoma (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192). Mortality from all cancers combined was slightly but significantly elevated in the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence interval, 121 to 176). This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies. Conclusions about an increase in the risk of soft-tissue sarcoma are limited by small numbers and misclassification on death certificates.

  15. Time-domain multimode dispersion measurement in a higher-order-mode fiber.

    PubMed

    Cheng, Ji; Pedersen, Martin E V; Wang, Ke; Xu, Chris; Grüner-Nielsen, Lars; Jakobsen, Dan

    2012-02-01

    We present a new multimode dispersion measurement technique based on the time-of-flight method. The modal delay and group velocity dispersion of all excited modes in a few-mode fiber can be measured simultaneously by a tunable pulsed laser and a high speed sampling oscilloscope. A newly designed higher-order-mode fiber with large anomalous dispersion in the LP(02) mode has been characterized using this method, and experimental results are in good agreement with the designed dispersion values. The demonstrated technique is significantly simpler to implement than the existing frequency-domain or interferometry-based methods.

  16. Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function.

    PubMed

    Hood, Darryl B; Woods, Letha; Brown, La'nissa; Johnson, Salynn; Ebner, Ford F

    2006-12-01

    Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex.

  17. Maxwell times in higher-order generalized hydrodynamics: Classical fluids, and carriers and phonons in semiconductors.

    PubMed

    Rodrigues, Clóves G; Silva, Carlos A B; Ramos, José G; Luzzi, Roberto

    2017-02-01

    A family of what can be so-called Maxwell times which arises in the context of higher-order generalized hydrodynamics (HOGH; also called mesoscopic hydrothermodynamics) is evidenced. This is done in the framework of a HOGH built within a statistical formalism in terms of a nonequilibrium statistical ensemble formalism. It consists in a description in terms of the densities of particles and energy and their fluxes of all orders, with the motion described by a set of coupled nonlinear integro-differential equations involving them. These Maxwell times have a fundamental role in determining the type of hydrodynamic motion that the system would display in the given conditions and constraints. They determine a Maxwell viscous force not present in the usual hydrodynamic equations, for example, in Navier-Stokes equation.

  18. Maxwell times in higher-order generalized hydrodynamics: Classical fluids, and carriers and phonons in semiconductors

    NASA Astrophysics Data System (ADS)

    Rodrigues, Clóves G.; Silva, Carlos A. B.; Ramos, José G.; Luzzi, Roberto

    2017-02-01

    A family of what can be so-called Maxwell times which arises in the context of higher-order generalized hydrodynamics (HOGH; also called mesoscopic hydrothermodynamics) is evidenced. This is done in the framework of a HOGH built within a statistical formalism in terms of a nonequilibrium statistical ensemble formalism. It consists in a description in terms of the densities of particles and energy and their fluxes of all orders, with the motion described by a set of coupled nonlinear integro-differential equations involving them. These Maxwell times have a fundamental role in determining the type of hydrodynamic motion that the system would display in the given conditions and constraints. They determine a Maxwell viscous force not present in the usual hydrodynamic equations, for example, in Navier-Stokes equation.

  19. Time-Domain Analysis of Higher Order Mode Properties in an Open Cavity Retaining Axial Symmetry

    NASA Astrophysics Data System (ADS)

    Lin, S. Y.; Lin, M. C.

    2016-10-01

    Theoretical and computational research to accurately and efficiently determine higher order mode properties of an axially symmetrical open cavity has been pursued. Open cavities have been widely employed in gyrotrons for the generation of high-power millimeter, submillimeter, and THz waves. A standing wave forms in the main body of the cavity, and the open end allows the extraction of power generated by the electron beam wave interaction. On the other hand, microresonators, such as microspheres that have small effective volume of their whispering gallery modes (WGMs), high quality factors, and quasi insensitivity to conducting material boundaries can also be considered as open cavities since the WGMs are natural electromagnetic eigenmodes that are activated by external coherent signals. For these cavities, axial symmetry is usually retained. The CAVITY program developed by Professor K. R. Chu using Fortran allows the users to accurately and efficiently determine the resonant frequency, the quality factor, and the field profile for the TE modes of an open cavity. In this work, an extension of the CAVITY program using Mathematica, CAVITY-M, to perform time-domain analysis of higher order modes in open cavities retaining axial symmetry for wider applications such as those mentioned above has been carried out. The new CAVITY-M program developed using Mathematica is able to effectively analyze the higher order mode characteristics of a general open cavity with an axial symmetry, in addition to the traditional modes in a gyrotron cavity.

  20. Higher Order Time Integration Schemes for the Unsteady Navier-Stokes Equations on Unstructured Meshes

    NASA Technical Reports Server (NTRS)

    Jothiprasad, Giridhar; Mavriplis, Dimitri J.; Caughey, David A.; Bushnell, Dennis M. (Technical Monitor)

    2002-01-01

    The efficiency gains obtained using higher-order implicit Runge-Kutta schemes as compared with the second-order accurate backward difference schemes for the unsteady Navier-Stokes equations are investigated. Three different algorithms for solving the nonlinear system of equations arising at each timestep are presented. The first algorithm (NMG) is a pseudo-time-stepping scheme which employs a non-linear full approximation storage (FAS) agglomeration multigrid method to accelerate convergence. The other two algorithms are based on Inexact Newton's methods. The linear system arising at each Newton step is solved using iterative/Krylov techniques and left preconditioning is used to accelerate convergence of the linear solvers. One of the methods (LMG) uses Richardson's iterative scheme for solving the linear system at each Newton step while the other (PGMRES) uses the Generalized Minimal Residual method. Results demonstrating the relative superiority of these Newton's methods based schemes are presented. Efficiency gains as high as 10 are obtained by combining the higher-order time integration schemes with the more efficient nonlinear solvers.

  1. Time-dependent treatment of electron-hydrogen scattering for higher angular momenta (L>0)

    NASA Astrophysics Data System (ADS)

    Odero, D. O.; Peacher, J. L.; Schultz, D. R.; Madison, D. H.

    2001-02-01

    The time-dependent approach to electron-atom scattering is emerging as an alternative to more conventional methods of treating atomic collisions. Solving the time-dependent Schrödinger equation directly has several very attractive features including a completely nonperturbative solution, dense representation of the nonphysical positive energy states, circumvention of the need to explicitly impose boundary conditions for ionization, and the convenience of being able to ``watch'' the electronic probability density evolve though the collision. Two principal approaches have so far been applied to treat electron-atom scattering, namely, the time-dependent close couping (TDCC) method and what we refer to as the time-dependent Hylleraas (TDH) method. The TDCC method solves coupled equations with two variables within a truncated infinite sum over individual angular momenta for each total angular momentum L of the system. In contrast, the TDH method avoids an infinite summation over the angular momenta of the individual electrons at the expense of solving a coupled equation with three variables for each L. The TDH method has previously been used for L=0 only. An important question, therefore, concerns whether the TDH method would represent a numerical advantage over the TDCC method for higher L values. This issue is investigated in this paper.

  2. Higher Order Time Integration Schemes for the Unsteady Navier-Stokes Equations on Unstructured Meshes

    NASA Technical Reports Server (NTRS)

    Jothiprasad, Giridhar; Mavriplis, Dimitri J.; Caughey, David A.

    2002-01-01

    The rapid increase in available computational power over the last decade has enabled higher resolution flow simulations and more widespread use of unstructured grid methods for complex geometries. While much of this effort has been focused on steady-state calculations in the aerodynamics community, the need to accurately predict off-design conditions, which may involve substantial amounts of flow separation, points to the need to efficiently simulate unsteady flow fields. Accurate unsteady flow simulations can easily require several orders of magnitude more computational effort than a corresponding steady-state simulation. For this reason, techniques for improving the efficiency of unsteady flow simulations are required in order to make such calculations feasible in the foreseeable future. The purpose of this work is to investigate possible reductions in computer time due to the choice of an efficient time-integration scheme from a series of schemes differing in the order of time-accuracy, and by the use of more efficient techniques to solve the nonlinear equations which arise while using implicit time-integration schemes. This investigation is carried out in the context of a two-dimensional unstructured mesh laminar Navier-Stokes solver.

  3. Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

    PubMed Central

    Han, Mei; Zhang, Ji-chun; Hashimoto, Kenji

    2017-01-01

    Objective Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA. PMID:28138113

  4. Immunohistochemistry of cytokeratins 7, 8, 17, 18, and 19, and GLUT-1 aids differentiation of desmoplastic malignant mesothelioma from fibrous pleuritis.

    PubMed

    Horiuchi, Toshikatsu; Ogata, Sho; Tominaga, Susumu; Hiroi, Sadayuki; Kawahara, Kunimitsu; Hebisawa, Akira; Irei, Isao; Ito, Ichiro; Kameya, Toru; Tsujimura, Tohru; Nakano, Takashi; Nakanishi, Kuniaki; Kawai, Toshiaki

    2013-05-01

    It is difficult to distinguish desmoplastic malignant mesothelioma (DMM) from fibrous pleuritis (FP). We investigated the utility of immunohistochemistry as a way of differentiating between DMM and FP. We examined 11 DMMs and 46 FPs with the aid of antibodies against 18 cytokeratin (CK) subtypes, calponin, caldesmon, desmin, and GLUT-1. The best sensitivity and specificity cut-off values in the receiver operating characteristic curves (ROC) for CKs 7, 8, 17, 18, and 19, and GLUT-1 were each above 60%. When cases with either DMM or FP were partitioned by the staining score associated with the best sensitivity and specificity cut-off values in ROC, the incidence of a positive expression for CKs 7, 8, 17, 18, and 19, and GLUT-1 was significantly higher in DMM than in FP. In conclusion, immunohistochemistry for CKs 7, 8, 17, 18, and 19, and GLUT-1 may be useful, alongside histological characteristics, for separating DMM from FP.

  5. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

    PubMed Central

    Dowling, David J.; van Haren, Simon D.; Scheid, Annette; Bergelson, Ilana; Kim, Dhohyung; Mancuso, Christy J.; Foppen, Willemina; Fresh, Lynn; Theriot, Terese B.; Lackner, Andrew A.; Fichorova, Raina N.; Smirnov, Dmitri; Vasilakos, John P.; Beaurline, Joe M.; Tomai, Mark A.; Midkiff, Cecily C.; Alvarez, Xavier; Blanchard, James L.; Gilbert, Margaret H.; Aye, Pyone Pyone

    2017-01-01

    Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197–specific neonatal CD4+ cells, activation of newborn and infant Streptococcus pneumoniae polysaccharide–specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10–100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development. PMID:28352660

  6. 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

    PubMed Central

    Chang, Hsin-An; Wang, Ying-Hsiu; Tung, Che-Se; Yeh, Chin-Bin

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. Methods SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. Results Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. Conclusion 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression. PMID:27757132

  7. 40 CFR 180.1283 - (Z)-7,8-epoxy-2-methyloctadecane (Disparlure); exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false (Z)-7,8-epoxy-2-methyloctadecane... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1283 (Z)-7,8-epoxy-2-methyloctadecane... is established for residues of (Z)-7,8-epoxy-2-methyloctadecane on all food and feed crops that...

  8. 40 CFR 180.1283 - (Z)-7,8-epoxy-2-methyloctadecane (Disparlure); exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false (Z)-7,8-epoxy-2-methyloctadecane... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1283 (Z)-7,8-epoxy-2-methyloctadecane... is established for residues of (Z)-7,8-epoxy-2-methyloctadecane on all food and feed crops that...

  9. 40 CFR 180.1283 - (Z)-7,8-epoxy-2-methyloctadecane (Disparlure); exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false (Z)-7,8-epoxy-2-methyloctadecane... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1283 (Z)-7,8-epoxy-2-methyloctadecane... is established for residues of (Z)-7,8-epoxy-2-methyloctadecane on all food and feed crops that...

  10. 40 CFR 180.1283 - (Z)-7,8-epoxy-2-methyloctadecane (Disparlure); exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false (Z)-7,8-epoxy-2-methyloctadecane... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1283 (Z)-7,8-epoxy-2-methyloctadecane... is established for residues of (Z)-7,8-epoxy-2-methyloctadecane on all food and feed crops that...

  11. 40 CFR 180.1283 - (Z)-7,8-epoxy-2-methyloctadecane (Disparlure); exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false (Z)-7,8-epoxy-2-methyloctadecane... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1283 (Z)-7,8-epoxy-2-methyloctadecane... is established for residues of (Z)-7,8-epoxy-2-methyloctadecane on all food and feed crops that...

  12. The American Indian Social Studies Curriculum Activity Guide, Grades 7-8.

    ERIC Educational Resources Information Center

    Stutzman, Esther

    An attempt to add substance to history, the curriculum guide for grades 7-8 presents in 12 culture guides information on American Indians for teachers to use as supplement materials to social studies texts. Each culture guide is accompanied with a teacher guide offering activities or discussion/quiz questions. Topics of culture guides encompass…

  13. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY AND ITS RELATIONSHIP TO CANCER

    EPA Science Inventory

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other ...

  14. Health Risk Assessment Approach for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Draft)

    EPA Science Inventory

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects v...

  15. The effect of 7, 8-Methylenedioxylycoctonine -Type Diterpenoid Alkaloids on the Toxicity of Methyllycaconitine in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Larkspur plants contain numerous norditerpenoid alkaloids which include the 7, 8-methylenedioxylycoctonine (MDL-type) alkaloids and the N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) alkaloids. The MSAL-type alkaloids are generally much more toxic (typically > 20x). The toxicity of many t...

  16. Toxics in My Home? You Bet! Curriculum on Household Toxics for Grades 7-8.

    ERIC Educational Resources Information Center

    Purin, Gina; And Others

    This curriculum consists of a one-week course of study designed to introduce students in grades 7-8 to (or increase their awareness of) toxic substances commonly found in the home. It includes an introduction/conceptual framework, four lessons, a unit test, and appendices. Each lesson consists of a statement of purpose, objectives,…

  17. Close-up of 7/8' gold-plated liquid oxygen post plug

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Engineers are investigating the possibility that a 7/8' gold- plated liquid oxygen post plug became dislodged and created three small holes in the liquid hydrogen tubes inside the nozzle on main engine No. 3 on Space Shuttle Columbia. The holes caused a hydrogen leak during the STS-93 launch of Columbia on July 23.

  18. Mechanism of inhibition of GluA2 AMPA receptor channel opening by 2,3-benzodiazepine derivatives: functional consequences of replacing a 7,8-methylenedioxy with a 7,8-ethylenedioxy moiety.

    PubMed

    Qneibi, Mohammad S; Micale, Nicola; Grasso, Silvana; Niu, Li

    2012-02-28

    2,3-Benzodiazepine (2,3-BDZ) compounds are a group of AMPA receptor inhibitors and are drug candidates for treating neurological diseases involving excessive AMPA receptor activity. We investigated the mechanism by which GluA2Q(flip) receptor channel opening is inhibited by two 2,3-BDZ derivatives, i.e., 1-(4-aminophenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (2,3-BDZ-11-2) and its 1-(4-amino-3-chlorophenyl) analogue (2,3-BDZ-11-4). Both compounds have a 7,8-ethylenedioxy moiety instead of the 7,8-methylenedioxy feature present in the structure of GYKI 52466, the prototypic 2,3-BDZ compound. Using a laser-pulse photolysis approach with a time resolution of ~60 μs and a rapid solution flow technique, we characterized the effect of the two compounds on the channel opening process of the homomeric GluA2Q(flip) receptor. We found that both 2,3-BDZ-11-2 and 2,3-BDZ-11-4 are noncompetitive inhibitors with specificity for the closed-channel conformation of the GluA2Q(flip) receptor. However, 2,3-BDZ-11-4 is ~10-fold stronger, defined by its inhibition constant for the closed-channel conformation (i.e., K(I) = 2 μM), than 2,3-BDZ-11-2. From double-inhibitor experiments, we determined that both compounds bind to the same site, but this site is different from two other known, noncompetitive binding sites on the GluA2Q(flip) receptor previously reported. Our results provide both mechanistic clues to improve our understanding of AMPA receptor regulation and a structure-activity relationship for designing more potent 2,3-BDZ compounds with predictable properties for this new noncompetitive site.

  19. Pulse transmission receiver with higher-order time derivative pulse generator

    DOEpatents

    Dress, Jr., William B.; Smith, Stephen F.

    2003-08-12

    Systems and methods for pulse-transmission low-power communication modes are disclosed. A pulse transmission receiver includes: a front-end amplification/processing circuit; a synchronization circuit coupled to the front-end amplification/processing circuit; a clock coupled to the synchronization circuit; a trigger signal generator coupled to the clock; and at least one higher-order time derivative pulse generator coupled to the trigger signal generator. The systems and methods significantly reduce lower-frequency emissions from pulse transmission spread-spectrum communication modes, which reduces potentially harmful interference to existing radio frequency services and users and also simultaneously permit transmission of multiple data bits by utilizing specific pulse shapes.

  20. Statistical monitoring of aftershock sequences: a case study of the 2015 Mw7.8 Gorkha, Nepal, earthquake

    NASA Astrophysics Data System (ADS)

    Ogata, Yosihiko; Tsuruoka, Hiroshi

    2016-03-01

    Early forecasting of aftershocks has become realistic and practical because of real-time detection of hypocenters. This study illustrates a statistical procedure for monitoring aftershock sequences to detect anomalies to increase the probability gain of a significantly large aftershock or even an earthquake larger than the main shock. In particular, a significant lowering (relative quiescence) in aftershock activity below the level predicted by the Omori-Utsu formula or the epidemic-type aftershock sequence model is sometimes followed by a large earthquake in a neighboring region. As an example, we detected significant lowering relative to the modeled rate after approximately 1.7 days after the main shock in the aftershock sequence of the Mw7.8 Gorkha, Nepal, earthquake of April 25, 2015. The relative quiescence lasted until the May 12, 2015, M7.3 Kodari earthquake that occurred at the eastern end of the primary aftershock zone. Space-time plots including the transformed time can indicate the local places where aftershock activity lowers (the seismicity shadow). Thus, the relative quiescence can be hypothesized to be related to stress shadowing caused by probable slow slips. In addition, the aftershock productivity of the M7.3 Kodari earthquake is approximately twice as large as that of the M7.8 main shock.

  1. Immunological abnormalities 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed Central

    Jennings, A M; Wild, G; Ward, J D; Ward, A M

    1988-01-01

    Eighteen workers were reviewed 17 years after accidental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Clinical assessment showed that they were in good health. A study of several biochemical and immunological parameters in these subjects and in 15 carefully matched controls showed no difference in serum concentrations of hepatic enzymes between exposed workers and controls. Although mean serum concentrations of cholesterol and triglyceride were higher in exposed subjects than in controls, the results did not reach statistical significance. Antinuclear antibodies and immune complexes were detected significantly more frequently in the peripheral blood of workers exposed to dioxin. There was no significant difference between exposed workers and controls in the number of T lymphocytes, B lymphocytes, and helper and suppressor T cell counts in peripheral blood, but the number of natural killer cells identified by the monoclonal antibody Leu-7 was significantly higher in workers exposed to dioxin. PMID:3264183

  2. Fission Multiplicity Detection with Temporal Gamma-Neutron Discrimination from Higher-Order Time Correlation Statistics

    SciTech Connect

    Oberer, Richard B.

    2002-10-01

    The current practice of nondestructive assay (NDA) of fissile materials using neutrons is dominated by the 3He detector. This has been the case since the mid 1980s when Fission Multiplicity Detection (FMD) was replaced with thermal well counters and neutron multiplicity counting (NMC). The thermal well counters detect neutrons by neutron capture in the 3He detector subsequent to moderation. The process of detection requires from 30 to 60 μs. As will be explained in Section 3.3 the rate of detecting correlated neutrons (signal) from the same fission are independent of this time but the rate of accidental correlations (noise) are proportional to this time. The well counters are at a distinct disadvantage when there is a large source of uncorrelated neutrons present from (α, n) reactions for example. Plastic scintillating detectors, as were used in FMD, require only about 20 ns to detect neutrons from fission. One thousandth as many accidental coincidences are therefore accumulated. The major problem with the use of fast-plastic scintillation detectors, however, is that both neutrons and gamma rays are detected. The pulses from the two are indistinguishable in these detectors. For this thesis, a new technique was developed to use higher-order time correlation statistics to distinguish combinations of neutron and gamma ray detections in fast-plastic scintillation detectors. A system of analysis to describe these correlations was developed based on simple physical principles. Other sources of correlations from non-fission events are identified and integrated into the analysis developed for fission events. A number of ratios and metric are identified to determine physical properties of the source from the correlations. It is possible to determine both the quantity being measured and detection efficiency from these ratios from a single measurement without a separate calibration. To account for detector dead-time, an alternative analytical technique

  3. Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis.

    PubMed

    Nesnow, Stephen; Nelson, Garret; Padgett, William T; George, Michael H; Moore, Tanya; King, Leon C; Adams, Linda D; Ross, Jeffrey A

    2010-07-30

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-7,8-dihydroxy-7,8-dihydroB[a]P-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: (1) the induction of apurinic sites from radical cation processes, and (2) the metabolic formation of B[a]P-7,8-quinone (BPQ) that can form covalent DNA adducts or reactive oxygen species which can damage DNA. The studies presented here sought to examine the role of stable BPQ-DNA adducts in B[a]P-induced mouse lung tumorigenesis. Male strain A/J mice were injected intraperitoneally once with BPQ or trans-7,8-dihydroxy-7,8-dihydroB[a]P (BP-7,8-diol) at 30, 10, 3, or 0mg/kg. Lungs and livers were harvested after 24h, the DNA extracted and subjected to (32)P-postlabeling analysis. Additional groups of mice were dosed once with BPQ or BP-7,8-diol each at 30 mg/kg and tissues harvested 48 and 72 h later, or with B[a]P (50mg/kg, a tumorigenic dose) and tissues harvested 72 h later. No BPQ or any other DNA adducts were observed in lung or liver tissues 24, 48, or 72 h after the treatment with 30 mg/kg BPQ. BP-7,8-diol gave BPDE-DNA adducts at all time points in both tissues and B[a]P treatment gave BPDE-DNA adducts in the lung. In each case, no BPQ-DNA adducts were detected. Mouse body weights significantly decreased over time after BPQ or BP-7,8-diol treatments suggesting that systemic toxicity was induced by both agents. Model studies with BPQ and N-acetylcysteine suggested that BPQ is rapidly inactivated by sulfhydryl-containing compounds and not available for DNA adduction. We conclude that under these treatment conditions BPQ does not form stable covalent DNA adducts in the lungs or livers of strain A/J mice, suggesting that stable BPQ-covalent adducts are not a part of the complex of mechanisms involved in B[a]P-induced mouse lung tumorigenesis.

  4. 8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation.

    PubMed

    Hu, Chiung-Wen; Cooke, Marcus S; Tsai, Yi-Hung; Chao, Mu-Rong

    2015-02-01

    8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations.

  5. A novel fast gas chromatography method for higher time resolution measurements of speciated monoterpenes in air

    NASA Astrophysics Data System (ADS)

    Jones, C. E.; Kato, S.; Nakashima, Y.; Kajii, Y.

    2014-05-01

    Biogenic emissions supply the largest fraction of non-methane volatile organic compounds (VOC) from the biosphere to the atmospheric boundary layer, and typically comprise a complex mixture of reactive terpenes. Due to this chemical complexity, achieving comprehensive measurements of biogenic VOC (BVOC) in air within a satisfactory time resolution is analytically challenging. To address this, we have developed a novel, fully automated Fast Gas Chromatography (Fast-GC) based technique to provide higher time resolution monitoring of monoterpenes (and selected other C9-C15 terpenes) during plant emission studies and in ambient air. To our knowledge, this is the first study to apply a Fast-GC based separation technique to achieve quantification of terpenes in ambient air. Three chromatography methods have been developed for atmospheric terpene analysis under different sampling scenarios. Each method facilitates chromatographic separation of selected BVOC within a significantly reduced analysis time compared to conventional GC methods, whilst maintaining the ability to quantify individual monoterpene structural isomers. Using this approach, the C9-C15 BVOC composition of single plant emissions may be characterised within a 14.5 min analysis time. Moreover, in-situ quantification of 12 monoterpenes in unpolluted ambient air may be achieved within an 11.7 min chromatographic separation time (increasing to 19.7 min when simultaneous quantification of multiple oxygenated C9-C10 terpenoids is required, and/or when concentrations of anthropogenic VOC are significant). These analysis times potentially allow for a twofold to fivefold increase in measurement frequency compared to conventional GC methods. Here we outline the technical details and analytical capability of this chromatographic approach, and present the first in-situ Fast-GC observations of 6 monoterpenes and the oxygenated BVOC (OBVOC) linalool in ambient air. During this field deployment within a suburban forest

  6. Higher-order time integration of Coulomb collisions in a plasma using Langevin equations

    DOE PAGES

    Dimits, A. M.; Cohen, B. I.; Caflisch, R. E.; ...

    2013-02-08

    The extension of Langevin-equation Monte-Carlo algorithms for Coulomb collisions from the conventional Euler-Maruyama time integration to the next higher order of accuracy, the Milstein scheme, has been developed, implemented, and tested. This extension proceeds via a formulation of the angular scattering directly as stochastic differential equations in the two fixed-frame spherical-coordinate velocity variables. Results from the numerical implementation show the expected improvement [O(Δt) vs. O(Δt1/2)] in the strong convergence rate both for the speed |v| and angular components of the scattering. An important result is that this improved convergence is achieved for the angular component of the scattering if andmore » only if the “area-integral” terms in the Milstein scheme are included. The resulting Milstein scheme is of value as a step towards algorithms with both improved accuracy and efficiency. These include both algorithms with improved convergence in the averages (weak convergence) and multi-time-level schemes. The latter have been shown to give a greatly reduced cost for a given overall error level when compared with conventional Monte-Carlo schemes, and their performance is improved considerably when the Milstein algorithm is used for the underlying time advance versus the Euler-Maruyama algorithm. A new method for sampling the area integrals is given which is a simplification of an earlier direct method and which retains high accuracy. Lastly, this method, while being useful in its own right because of its relative simplicity, is also expected to considerably reduce the computational requirements for the direct conditional sampling of the area integrals that is needed for adaptive strong integration.« less

  7. Higher-order time integration of Coulomb collisions in a plasma using Langevin equations

    SciTech Connect

    Dimits, A. M.; Cohen, B. I.; Caflisch, R. E.; Rosin, M. S.; Ricketson, L. F.

    2013-02-08

    The extension of Langevin-equation Monte-Carlo algorithms for Coulomb collisions from the conventional Euler-Maruyama time integration to the next higher order of accuracy, the Milstein scheme, has been developed, implemented, and tested. This extension proceeds via a formulation of the angular scattering directly as stochastic differential equations in the two fixed-frame spherical-coordinate velocity variables. Results from the numerical implementation show the expected improvement [O(Δt) vs. O(Δt1/2)] in the strong convergence rate both for the speed |v| and angular components of the scattering. An important result is that this improved convergence is achieved for the angular component of the scattering if and only if the “area-integral” terms in the Milstein scheme are included. The resulting Milstein scheme is of value as a step towards algorithms with both improved accuracy and efficiency. These include both algorithms with improved convergence in the averages (weak convergence) and multi-time-level schemes. The latter have been shown to give a greatly reduced cost for a given overall error level when compared with conventional Monte-Carlo schemes, and their performance is improved considerably when the Milstein algorithm is used for the underlying time advance versus the Euler-Maruyama algorithm. A new method for sampling the area integrals is given which is a simplification of an earlier direct method and which retains high accuracy. Lastly, this method, while being useful in its own right because of its relative simplicity, is also expected to considerably reduce the computational requirements for the direct conditional sampling of the area integrals that is needed for adaptive strong integration.

  8. Renewing Quality Assurance at a Time of Turbulence: An Attempt to Reenergise Quality in Australian Higher Education

    ERIC Educational Resources Information Center

    Shah, Mahsood; Nair, Chenicheri Sid

    2011-01-01

    The renewal of quality assurance in Australian higher education comes at a time when the higher education sectors in Australia and around the world are experiencing a number of key challenges. These include: ongoing decline in public funding of universities; the massification of higher education and demand for it during global recession;…

  9. Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine oxidation.

    PubMed

    White, Blánaid; Tarun, Maricar C; Gathergood, Nicholas; Rusling, James F; Smyth, Malcolm R

    2005-12-01

    8-Oxo-7,8-dihydroguanine (8-oxoGua), an important biomarker of DNA damage in oxidatively generated stress, is highly reactive towards further oxidation. Much work has been carried out to investigate the oxidation products of 8-oxoGua by one-electron oxidants, singlet oxygen, and peroxynitrite. This report details for the first time, the iron- and copper-mediated Fenton oxidation of 8-oxoGua and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Oxidised guanidinohydantoin (Gh(ox)) was detected as the major product of oxidation of 8-oxoGua with iron or copper and hydrogen peroxide, both at pH 7 and pH 11. Oxaluric acid was identified as a final product of 8-oxoGua oxidation. 8-oxodGuo was subjected to oxidation under the same conditions as 8-oxoGua. However, dGh(ox) was not generated. Instead, spiroiminodihydantoin (Sp) was detected as the major product for both iron and copper mediated oxidation at pH 7. It was proposed that the oxidation of 8-oxoGua was initiated by its one-electron oxidation by the metal species, which leads to the reactive intermediate 8-oxoGua (+), which readily undergoes further oxidation. The product of 8-oxoGua and 8-oxodGuo oxidation was determined by the 2'-deoxyribose moiety of the 8-oxodGuo, not whether copper or iron was the metal involved in the oxidation.

  10. Bouncebacks in Higher Education Funding: Patterns in Length of Time to Recovery following Cuts in State Appropriations. WISCAPE Policy Brief

    ERIC Educational Resources Information Center

    Doyle, William R.; Delaney, Jennifer A.

    2011-01-01

    State appropriations for higher education are highly cyclical, with downturns in funding during difficult financial times followed by increases in funding when state finances improve. This policy brief shares recent research about whether the duration of recoveries from cuts in appropriations for higher education has changed over time and which…

  11. Earthquake Forecasts for Gorkha Immediately Following the 25th April, M=7.8 Mainshock

    NASA Astrophysics Data System (ADS)

    Segkou, M.; Parsons, T.

    2015-12-01

    The M-7.8 Gorkha (Nepal) earthquake on the 25th April, 2015 has shaken the central Himalayan front and immediately raised concerns for the severity of future triggered earthquakes. Here, we implement standard and innovative forecast models to predict the spatio-temporal distribution of triggered events. Key challenges addressed are: 1) the limited information on early aftershocks, 2) the low-productivity aftershock sequence in the near-source area, 3) the off-fault (>250 km) triggered events exemplified by the M=5.4 Xegar event, 3 hrs after the mainshock. We apply short-term empirical/statistical ETAS and physical forecast models, the latter based on the combination of rate/state friction law and Coulomb stresses. Within the physics-based model implementation we seek to evaluate the uncertainty related with the rupture style of triggered events by considering: 1) the geometry of active structures, 2) optimally oriented for failure faults and 3) all-potential faults described by the total stress field. The latter is represented by the full stress tensor before and after the mainshock and our analysis suggests that the preseismic stress magnitudes are still sufficient to cause earthquakes even after modification by the mainshock. The above remark reveals that there are no "stress shadows" affecting the spatial distribution of near-field aftershocks. It is also noted that the method allows for an a-priori determination of the rupture plan of the M=7.3 event, within the limit of uncertainty (20˚). The results show that: (1) ETAS models underestimate the number of observed events, since they heavily base their good performance in small magnitude earthquakes, not available in the first few weeks after the mainshock, (2) far field triggered events are captured only by physics-based forecasts, and (3) the total stress method improves the predictability of larger magnitude events. We conclude that frontier regions benefit from the implementation of physics-based models

  12. In Ovo 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure in Three Avian Species

    PubMed

    Janz; Bellward

    1996-08-01

    As opposed to mammals, the heterogametic sex in birds is female, and sexual differentiation of the central nervous system away from the intrinsic male pattern is dependent on ovarian estrogen secretions during the perinatal period. The contamination of aquatic systems with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds has been suggested to be responsible for decreased reproductive success in certain wild fish-eating bird populations. Since TCDD has been shown to alter estrogenic status in laboratory animals, we determined the effects of in ovo TCDD exposure on hepatic estrogen receptor (ER) concentrations and affinities, and plasma estradiol concentrations during the perinatal period in the domestic chicken (Gallus gallus), domestic pigeon (Columba livia), and great blue heron (Ardea herodias). Plasma testosterone levels were also determined in herons as an indication of androgenic status. [3H]TCDD was injected into the air cell of chicken eggs on Embryonic Day 4.5 (0.1 μg/kg egg), pigeon eggs on Embryonic Day 3.5 (1 μg/kg egg) and Embryonic Day 14 (3 μg/kg egg), and heron eggs at approximately Embryonic Day 13 (2 μg/kg egg). Chickens were euthanized on Embryonic Days 17 and 19, hatch, and Days 2 and 4 after hatch. Pigeons and herons were either euthanized at hatch or fed an uncontaminated diet for 7 days prior to termination. Between 5 and 10% of the injected [3H]TCDD dose was measured in the liver of hatchlings. There was no effect of in ovo TCDD exposure on hepatic ER levels or plasma estradiol concentrations in female chickens and pigeons exposed early in incubation. In female pigeons exposed during the latter third part of incubation to a TCDD dose that would cause high embryo lethality if injected early in incubation, hepatic ER concentrations were elevated (p < 0.001) and plasma estradiol concentrations were decreased (p < 0.01) at hatch. There was no effect of TCDD exposure on plasma estradiol levels in male pigeons. In herons, TCDD

  13. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation

    PubMed Central

    Li, Yan; Wang, Kai; Jiang, Yi-Zhou; Chang, Xin-Wen; Dai, Cai-Feng

    2017-01-01

    Purpose The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates a broad spectrum of biological processes, including ovarian growth and ovulation. Recently, we found that an endogenous AhR ligand (ITE) can inhibit ovarian cancer proliferation and migration via the AhR. Here, we tested whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an exogenous AhR ligand) may exert similar anti-ovarian cancer activities using human ovarian cancer and non-cancerous human ovarian surface epithelial cells. Methods Two human ovarian cancer cell lines (SKOV-3 and OVCAR-3) and one human ovarian surface epithelial cell line (IOSE-385) were used. Cell proliferation and migration activities were determined using crystal violet and FluoroBlok insert system assays, respectively. AhR protein expression was assessed by Western blotting. Expression of cytochrome P450, family 1, member A1 (CYP1A1) and member B1 (CYP1B1) mRNA was assessed by qPCR. Small interfering RNAs (siRNAs) were used to knock down AhR expression. Results We found that TCDD dose-dependently suppressed OVCAR-3 cell proliferation, with a maximum effect (~70 % reduction) at 100 nM. However, TCDD did not affect SKOV-3 and IOSE-385 cell proliferation and migration. The estimated IC50 of TCDD for inhibiting OVCAR-3 cell proliferation was 4.6 nM. At 10 nM, TCDD time-dependently decreased AhR protein levels, while it significantly increased CYP1A1 and CYP1B1 mRNA levels in SKOV-3, OVCAR-3 and IOSE-385 cells, indicating activation of AhR signaling. siRNA-mediated AhR knockdown readily blocked TCDD-mediated suppression of OVCAR-3 cell proliferation. Conclusion Our data indicate that TCDD can suppress human ovarian cancer cell proliferation via the AhR signaling pathway and that TCDD exhibits an anti-proliferative activity in at least a subset of human ovarian cancer cells. PMID:25404385

  14. 'Advancement of KHPS to DOE TRL 7/8' Project - Final Technical Report

    SciTech Connect

    Adonizio, Mary Ann; Corren, Dean; Smith, Ron; Colby, Jonathan; Hernandez, Aaron

    2016-04-08

    Final Report describing activities performed under the 'Advancement of the KHPS to DOE TRL 7/8' project, including the development of critical component test protocols, testing and analysis of the Gen5 KHPS main shaft seal, and continuing compliance work on approved operational environmental monitoring plans in anticipation of KHPS turbine installation at Verdant Power's Roosevelt Island Tidal Energy (RITE) Project site in New York, NY.

  15. 7.8 GHz High Power Generation And Extraction With A Dielectric-loaded Waveguide

    SciTech Connect

    Gao, F.; Conde, M. E.; Gai, W.; Konecny, R.; Liu, W.; Power, J. G.; Yusof, Z.; Jing, C.; Wong, T.

    2009-01-22

    In this paper, we present updated results on power extraction testing of a 7.8 GHz dielectric loaded waveguide power extractor using both high charge single bunches and bunch trains. We have generated a 1.7 ns radio frequency (rf) pulse with 30 MW of power with a single 66 nC electron bunch. Then we have generated a pulse train of electron beam for rf generation of 10 ns and 22 ns rf pulses.

  16. 7.8GHz High power generation and extraction with a dielectric-loaded waveguide.

    SciTech Connect

    Conde, M. E.; Gai, W.; Konecny, R.; Power, J. G.; Gao, F.; Wong, T.; Yusof, Z.; High Energy Physics; Illinois Inst. of Tech.; Euclid Techlabs

    2009-01-01

    In this paper, we present updated results on power extraction testing of a 7.8 GHz dielectric loaded waveguide power extractor using both high charge single bunches and bunch trains. We have generated a 1.7 ns radio frequency (rf) pulse with 30 MW of power with a single 66 nC electron bunch. Then we have generated a pulse train of electron beam for rf generation of 10 ns and 22 ns rf pulses.

  17. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors

    PubMed Central

    Tietz, Alexandra; Rahbari, Nuh N.; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A.; Lipson, Kenneth E.; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E.

    2015-01-01

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy. PMID:25609199

  18. 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders.

    PubMed

    Du, X; Hill, R A

    2015-10-01

    Neurodevelopmental disorders are a group of conditions that arises from impairments of the central nervous system during its development. The causes of the various disorders are heterogeneous and the symptoms likewise are multifarious. Most of these disorders currently have very little available treatment that is effective in combating the plethora of serious symptoms. Brain-derived neurotrophic factor (BDNF) is a fundamental neurotrophin with vital functions during brain development. Pre-clinical studies have shown that increasing BDNF signalling may be a potent way to prevent, arrest or even reverse abnormal neurodevelopmental events arising from a variety of genetic or environmental causes. However, many difficulties make BDNF problematic to administer in an efficient manner. The recent discovery of a small BDNF-mimetic, the naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF), may provide an avenue to allow efficient and safe activation of the BDNF pathway in tackling the symptoms of neurodevelopmental disorders. Here, evidence will be provided to support the potential of 7,8-DHF as a novel treatment for several neurodevelopmental disorders where the BDNF signalling pathway is implicated in the pathophysiology and where benefits are therefore most likely to be derived from its implementation.

  19. Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in Swiss-Webster Mice (Dermal Study).

    PubMed

    1982-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin occurs as a highly toxic impurity found in herbicides containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4,5-T- derivatives, as well as in other chemicals synthesized using 2,4,5-trichlorophenol. The herbicide 2,4,5-T has been marketed in the United States since 1948. Production increased sharply between 1960 and 1970 when a 1:1 mixture of 2,4,5-T and 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a defoliant in Vietnam under the names of "herbicide agent orange, herbicide orange, agent orange, and orange". During this 10-year period, about 106 million pounds of 2,4,5-T were sprayed. A carcinogenesis bioassay was conducted by applying an acetone suspension of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the clipped backs of 30 male and female Swiss-Webster mice 3 days per week for 99 or 104 weeks. Similar groups were pretreated with 1 application of 50 &mgr;g dimethylbenzanthracene (DMBA) in 0.1 ml acetone 1 week before TCDD administration began. Female mice received 0.005 &mgr;g TCDD per application, and the male mice received 0.001 &mgr;g TCDD. As vehicle controls, 45 mice of each sex received 0.1 ml acetone three times per week. Thirty animals of each sex were used as untreated controls. Throughout the bioassay, mean body weights of the male and female mice administered TCDD, or TCDD following DMBA, were essentially the same as those of the corresponding vehicle control group. Mean body weights of dosed and vehicle control groups of males were less thanthose of the untreated control group throughout the study; for the females, mean body weights were less than the untreated controls during the first 80 weeks. In female mice, the incidences of fibrosarcoma in the integumentary system in dosed groups with TCDD were significantly (P=0.007) higher than that in the corresponding controls (2/41, 5%; 8/27, 30%). An increase in the same tumor type, although not statistically significant (P=0.084), was also observed in

  20. Reflections on the Field of Higher Education: Time, Space and Sub-Fields

    ERIC Educational Resources Information Center

    Yokoyama, Keiko

    2016-01-01

    The objective of this study is to define the field of higher education and clarify its identity. It examines three analytical dimensions which, it proposes, shape the field: knowledge, approach and community. It argues that contextual knowledge around the issue of higher education has defined the field but has not determined techniques that are…

  1. The Changing Faces of Corruption in Georgian Higher Education: Access through Times and Tests

    ERIC Educational Resources Information Center

    Orkodashvili, Mariam

    2012-01-01

    This article presents a comparative-historical analysis of access to higher education in Georgia. It describes the workings of corrupt channels during the Soviet and early post-Soviet periods and the role of standardized tests in fighting corruption in higher education admission processes after introduction of the Unified National Entrance…

  2. Department Chairs' Perceptions of Part-Time Faculty Status in Maryland Public and Private Higher Education Institutions

    ERIC Educational Resources Information Center

    Moorehead, Daniel L.

    2011-01-01

    The growing use of part-time, non-tenure track faculty in higher education has become a nationwide phenomenon. The college-teaching part-time instructor is one who is working for low pay, has little job security, and has few benefits. College part-time instructors' employment is in a contingent state. They do not have the job protection provided…

  3. Young Adults with Head Trauma May Have Higher Risk of Jail Time

    MedlinePlus

    ... THURSDAY, Dec. 8, 2016 (HealthDay News) -- A traumatic brain injury may be linked to a young adult's higher ... These findings contribute to emerging research suggesting traumatic brain injury is an important risk factor for involvement with ...

  4. Part-Time Students and Part-Time Study in Higher Education in the UK: Strand 1--A Quantitative Data Analysis of 2003/04 HESA Data

    ERIC Educational Resources Information Center

    Ramsden, Brian

    2006-01-01

    This is a report of the Strand 1 element of the Universities UK project to examine part-time students and part-time study within the United Kingdom. The aim of Strand 1 of this project is to set out, as far as possible, factual information about students studying part-time and following programmes of study leading to higher education…

  5. The UT 7/8 February 2013 Sila-Nunam Mutual Event and Future Predictions

    NASA Technical Reports Server (NTRS)

    Benecchi, S. D.; Noll, K. S.; Thirouin, A.; Ryan, E.; Grundy, W. M.; Verbiscer, A.; Doressoundiram, A.; Hestroffer, D.; Beaton, R.; Rabinowitz, D.; Chanover, N.

    2013-01-01

    A superior mutual event of the Kuiper Belt binary system (79360) Sila-Nunam was observed over 15.47 h on UT 7/8 February 2013 by a coordinated effort at four different telescope facilities; it started approximately 1.5 h earlier than anticipated, the duration was approximately 9.5 h (about 10% longer than predicted), and was slightly less deep than predicted. It is the first full event observed for a comparably sized binary Kuiper Belt object. We provide predictions for future events refined by this and other partial mutual event observations obtained since the mutual event season began.

  6. Spectral imaging of the Orion Bar at 6.2 and 7.8 microns

    NASA Technical Reports Server (NTRS)

    Bregman, Jesse; Harker, David; Rank, David; Temi, Pasquale

    1995-01-01

    We have obtained images of the Orion Bar region through narrow-band filters at 6.2 and 7.8 mu m to determine whether the emission observed at these wavelengths arises from C-C modes in polycyclic aromatic hydrocarbons (PAH's). Morphologically, the distribution of the emissions are similar, but appear different in detail. Quantitative comparisons of these band intensities with previous data at 8.4 and 11.3 mu m indicates that they are indeed consistent with emission from fluorescently excited PAH molecules.

  7. Gene Deletion of 7,8-Linoleate Diol Synthase of the Rice Blast Fungus

    PubMed Central

    Jernerén, Fredrik; Sesma, Ane; Francheschetti, Marina; Hamberg, Mats; Oliw, Ernst H.

    2010-01-01

    Linoleate diol synthases (LDS) are heme enzymes, which oxygenate 18:2n-6 sequentially to (8R)-hydroperoxylinoleic acid ((8R)-HPODE) and to (5S,8R)-dihydroxy-, (7S,8S)-dihydroxy-, or (8R,11S)-dihydroxylinoleic acids (DiHODE). The genome of the rice blast fungus, Magnaporthe oryzae, contains two genes with homology to LDS. M. oryzae oxidized 18:2n-6 to (8R)-HPODE and to (7S,8S)-DiHODE, (6S,8R)-DiHODE, and (8R,11S)-HODE. Small amounts of 10-hydroxy-(8E,12Z)-octadecadienoic acid and traces of 5,8-DiHODE were also detected by liquid chromatography-mass spectrometry. The contribution of the 7,8-LDS gene to M. oryzae pathogenicity was evaluated by replacement of the catalytic domain with hygromycin and green fluorescent protein variant (SGFP) cassettes. This genetically modified strain Δ7,8-LDS infected rice leaves and roots and formed appressoria and conidia as the native fungus. The Δ7,8-LDS mutant had lost the capacity to biosynthesize all the metabolites except small amounts of 8-hydroxylinoleic acid. Studies with stereospecifically deuterated linoleic acids showed that (8R)-HPODE was formed by abstraction of the pro-S hydrogen at C-8 and antarafacial oxygenation, whereas (7S,8S)-DiHODE and (8R,11S)-DiHODE were formed from (8R)-HPODE by suprafacial hydrogen abstraction and oxygenation at C-7 and C-11, respectively. A mac1 suppressor mutant (Δmac1 sum1–99) of M. oryzae, which shows cAMP-independent protein kinase A activity, oxygenated 18:2n-6 to increased amounts of (10R)-HPODE and (5S,8R)-DiHODE. Expression of the 7,8-LDS gene but not of the second homologue was detected in the suppressor mutant. This suggests that PKA-mediated signaling pathway regulates the dioxygenase and hydroperoxide isomerase activities of M. oryzae. PMID:20023302

  8. A toxicological study of 5,6,7,8 tetrafluoro- 1,4-benzodioxin

    SciTech Connect

    London, J.E.

    1988-05-01

    The acute oral LD/sub 50/ values for 5,6,7,8 tetrafluro-1,4 benzodioxin for mice and rats are less than 5 gkg. According to classical guidelines, the material is considered slightly toxic in both species. The sensitization study in the guinea pig did not show the material to have potential sensitizing properties. Skin application studies on the rabbit demonstrated that it was cutaneously mildly irritating. This material was very mildly irritating in the rabbit eye application studies. 4 refs., 2 tabs.

  9. Synthesis and bioactivities of 6,7,8-trimethoxy-N-aryl-4-aminoquinazoline derivatives.

    PubMed

    Liu, Gang; Hu, De-Yu; Jin, Lin-Hong; Song, Bao-An; Yang, Song; Liu, Ping-Shen; Bhadury, Pinaki S; Ma, Yao; Luo, Hui; Zhou, Xian

    2007-10-15

    A series of 4-aminoquinazoline derivatives is prepared by the nucleophilic substitution reaction of 6,7,8-trimethoxy-4-chloroquinazoline and aryl amine. The structures of the compounds are confirmed by elemental analysis, IR, and (1)H NMR spectral data. The compounds are also evaluated for their ability to inhibit tumor cells PC3, A431, Bcap-37, and BGC823 by MTT assays. Among them, 6b and 6e are found as potent inhibitors, with IC(50) values ranging from 5.8 to 9.8microM, in vitro assay.

  10. Geotechnical effects of the 2015 magnitude 7.8 Gorkha, Nepal, earthquake and aftershocks

    USGS Publications Warehouse

    Moss, Robb E. S.; Thompson, Eric; Kieffer, D Scott; Tiwari, Binod; Hashash, Youssef M A; Acharya, Indra; Adhikari, Basanta; Asimaki, Domniki; Clahan, Kevin B.; Collins, Brian D.; Dahal, Sachindra; Jibson, Randall W.; Khadka, Diwakar; Macdonald, Amy; Madugo, Chris L M; Mason, H Benjamin; Pehlivan, Menzer; Rayamajhi, Deepak; Uprety, Sital

    2015-01-01

    This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes.

  11. The Impact of Part-Time Faculty on Student Retention: A Case Study in Higher Education

    ERIC Educational Resources Information Center

    Smith, Curtis V.

    2010-01-01

    There has been considerable debate in community colleges over the last forty years regarding the impact of increased use of part-time faculty (PTF) on student learning. It has been argued that part-time faculty fail to provide the same level of teaching quality as full-time faculty (FTF). The purpose of this study was to determine the impact of…

  12. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated gene expression in the immature rat thymus.

    PubMed

    Olnes, M J; Verma, M; Kurl, R N

    1994-01-01

    To examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic gene expression in vitro, freshly isolated rat thymocytes were incubated with 10 nM TCDD, and reverse transcriptase polymerase chain reaction experiments were performed using primers specific for prostaglandin G/H synthase (PGHS) and glyceraldehyde 3-phosphate dehydrogenase. TCDD selectively repressed PGHS gene expression, with maximal inhibition occurring within 60 min. Gel retardation assays demonstrated that dioxin transiently induced binding of the ubiquitous transcription factor NF kappa B to its cognate response element at early time points. However, TCDD had little ability to induce transformation of the Ah receptor to the xenobiotic responsive element in thymic cytosol. These results indicate that TCDD exerts changes in thymocyte gene expression prior to inducing toxicity.

  13. Thermal iron ions in high speed solar wind streams Detection by the IMP 7/8 energetic particle experiments

    NASA Technical Reports Server (NTRS)

    Mitchell, D. G.; Roelof, E. C.

    1980-01-01

    The first measurements of the abundance of iron ions in high speed (greater than 600 km/s) solar wind streams have been made with the NOAA/JHU energetic particles experiments (EPE) on IMP 7/8. The identification of iron ions is quantitatively established using 4 years of observations and heavy ion accelerator calibrations of detectors similar to those flown on the spacecraft. Preliminary estimates of the Fe/H ratio are within a factor of 2 of the adopted coronal abundance (0.00005), and there is some evidence that Fe/H may remain approximately constant within a given stream. In the peaks of fast streams (700-800 km/s), about 50 iron ion counts are obtained every 20 s, offering the possibility of studying the Fe/H ratio with approximately 1 m time resolution in high speed streams throughout the decline of Solar Cycle 20 and the rise of Solar Cycle 21.

  14. Hexachlorodibenzo-p-dioxin (HxCDD), mixture of 1,2,3,6,7,8-HxCDD and 1,2,3,7,8,9-HxCDD

    Integrated Risk Information System (IRIS)

    Hexachlorodibenzo - p - dioxin ( HxCDD ) , mixture of 1,2,3,6,7,8 - HxCDD and 1,2,3,7,8,9 - HxCDD ; CASRN 57653 - 85 - 7 and 19408 - 74 - 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

  15. Summary of External Peer Review and Public Comments and Disposition for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8,-hexamethylcyclopenta[γ]-2-benzopyran (HHCB)

    EPA Pesticide Factsheets

    This document summarizes the public and external peer review comments that the EPA’s Office of Pollution Prevention and Toxics (OPPT) received for the draft work plan risk assessment for 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta--2-benzopyran

  16. Effect of 7,8-dihydroxyflavone as an antioxidant on in vitro maturation of oocytes and development of parthenogenetic embryos in pigs.

    PubMed

    Choi, Ji-Yei; Kang, Jung-Taek; Park, Sol-Ji; Kim, Su-Jin; Moon, Joon-Ho; Saadeldin, Islam M; Jang, Goo; Lee, Byeong-Chun

    2013-10-01

    One of the factors that impairs in vitro produced porcine embryos is the oxidative stress that is mainly caused by the imbalance between reactive oxygen species (ROS) generation and antioxidants activity, especially that of glutathione (GSH). Here, we examined the effect of 7,8-dihydroxyflavone (7,8-DHF), a kind of flavonoid antioxidant, on porcine oocyte maturation and its developmental competence. Porcine oocytes were cultured in media supplemented with 0, 1, 5 and 10 μM 7,8-DHF during both in vitro maturation (IVM) and in vitro culture (IVC) after parthenogenetic activation. Maturation of oocytes was evaluated based on first polar body (PB) extrusion and intracellular GSH level, and developmental competence was assessed through observing cleavage and blastocyst formation. In each step, the levels of intracellular GSH and ROS were assessed by fluorescence intensity, and the apoptosis-related gene expression was examined using semiquantitative RT-PCR. The group treated with 1 μM 7,8-DHF during IVM and IVC showed increased cytoplasmic maturation and reached the blastocysts stage (36.1%) at a higher rate than the other groups (24.7, 16.0 and 10.3% for 0, 5 and 10 μM, P<0.05). In that group, the intracellular GSH level was significantly increased while ROS generation was significantly decreased after IVM and IVC (P<0.05). Moreover, it showed high expression of an anti-apoptotic gene (BCL2L1) and low expression of a pro-apoptotic gene (BAK1) (P<0.05). In conclusion, treatment with 1 μM 7,8-DHF during IVM and IVC showed an anti-apoptotic effect by increasing intracellular GSH synthesis and scavenging ROS and therefore improved the developmental competence of porcine embryos.

  17. Effect of 7,8-Dihydroxyflavone as an Antioxidant on In Vitro Maturation of Oocytes and Development of Parthenogenetic Embryos in Pigs

    PubMed Central

    CHOI, Ji-Yei; KANG, Jung-Taek; PARK, Sol-Ji; KIM, Su-Jin; MOON, Joon-Ho; SAADELDIN, Islam M.; JANG, Goo; LEE, Byeong-Chun

    2013-01-01

    One of the factors that impairs in vitro produced porcine embryos is the oxidative stress that is mainly caused by the imbalance between reactive oxygen species (ROS) generation and antioxidants activity, especially that of glutathione (GSH). Here, we examined the effect of 7,8-dihydroxyflavone (7,8-DHF), a kind of flavonoid antioxidant, on porcine oocyte maturation and its developmental competence. Porcine oocytes were cultured in media supplemented with 0, 1, 5 and 10 μM 7,8-DHF during both in vitro maturation (IVM) and in vitro culture (IVC) after parthenogenetic activation. Maturation of oocytes was evaluated based on first polar body (PB) extrusion and intracellular GSH level, and developmental competence was assessed through observing cleavage and blastocyst formation. In each step, the levels of intracellular GSH and ROS were assessed by fluorescence intensity, and the apoptosis-related gene expression was examined using semiquantitative RT-PCR. The group treated with 1 μM 7,8-DHF during IVM and IVC showed increased cytoplasmic maturation and reached the blastocysts stage (36.1%) at a higher rate than the other groups (24.7, 16.0 and 10.3% for 0, 5 and 10 μM, P<0.05). In that group, the intracellular GSH level was significantly increased while ROS generation was significantly decreased after IVM and IVC (P<0.05). Moreover, it showed high expression of an anti-apoptotic gene (BCL2L1) and low expression of a pro-apoptotic gene (BAK1) (P<0.05). In conclusion, treatment with 1 μM 7,8-DHF during IVM and IVC showed an anti-apoptotic effect by increasing intracellular GSH synthesis and scavenging ROS and therefore improved the developmental competence of porcine embryos. PMID:23748647

  18. Radiolytic degradation of 2,3,7,8-TCDD in artificially contaminated soils

    SciTech Connect

    Hillarides, R.J.; Gray, K.A. ); Guzzetta, J.; Cortellucci, N.; Sommer, C. )

    1994-12-01

    This paper reports results of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) destruction on artificially contaminated soil using cobalt-60 ([sup 60]Co) [gamma] radiation. Important parameters (soil moisture content, surfactant type/concentration, equilibration, and radiation dose) and their optimum ranges are identified. Scavenger (N[sub 2]O, O[sub 2], 2-propanol) studies were conducted to explore the consequences of controlling oxidative and reductive conditions in the soil, and reaction byproducts have been analyzed under selected reaction conditions. A standard soil (EPA SSM-91) was artificially contaminated with 2,3,7,8-TCDD to 100 ppb, and in the presence of 25% water and 2% surfactant (RA-40) and at a high irradiation dose (800 kGy), greater than 92% TCDD destruction was achieved, resulting in a final TCDD concentration of less than 7 ppb. Results of scavenger and byproduct studies and theoretical target theory calculations indicate that TCDD destruction is caused primarily by direct radiation effects and proceeds through reductive dechlorination. 53 refs., 6 figs., 3 tabs.

  19. Oxidation of benzo(a)pyrene-7,8-diol by methemoglobin and hydrogen peroxide

    SciTech Connect

    Catalano, C.E.; Ortiz, de Montellano, P.R.

    1986-05-01

    Methemoglobin catalyzes the hydrogen peroxide dependent oxidation of styrene to styrene oxide. An alkylperoxy radical formed from the combination of molecular oxygen with an amino acid radical at the protein surface has been proposed as the actual oxidant. This model predicts that access to the heme crevice is not a requirement for oxidation. The oxidation of benzo(a)pyrene-7.8-dihydro-diol, a substrate whose steric bulk makes access into the heme crevice unlikely, has been examined to further test this hypothesis. Anti-trans-benzo(a)pyrene-7,8,9,10-tetrol is isolated from the incubation of B(a)P-diol in the presence of methemoglobin and H/sub 2/O/sub 2/. The exclusive formation of this tetrol supports a peroxidative epoxidation mechanism analogous to that for lipid peroxy radical oxidation of the title compound. The oxidation of conjugated fatty acids by the methemoglobin/H/sub 2/O/sub 2/ system further supports the hypothesis that oxidation of compounds occurs at protein surface and not in the heme crevice as previously suspected.

  20. Discovery of Imidazoquinolines with Toll-Like Receptor 7/8 Independent Cytokine Induction

    PubMed Central

    2012-01-01

    Toll-like receptors (TLRs) are key targets in the design of immunomodulating agents for use as vaccine adjuvants and anticancer treatments. The imidazoquinolines, imiquimod and resiquimod, have been shown to activate TLR-7 and -8, which in turn induce cytokine production as part of the innate immune response. Herein, we report the synthesis and discovery of a C7-methoxycarbonyl derivative of imiquimod that stimulates cytokine production but is devoid of TLR-7/8 activity. Data are presented that shows that this analogue not only induces IL-12p40 and TNF production, similar to that of imiquimod and resiquimod, but greatly enhances the production of IL-1β, a key cytokine involved in the activation of CD4 T cells. It is further demonstrated that TLR-7/8 activation can be recovered by the addition of a C2-alkyl substituent to this newly discovered analogue. The results support the existence of an alternative mechanism of action by which imidazoquinolines can stimulate cytokine production. PMID:22837811

  1. 2,3,7,8-DIBENZO-P-DIOXINS IN MINED CLAY PRODUCTS ...

    EPA Pesticide Factsheets

    Ball clay was the source of dioxin contamination discovered in selected chickens analyzed as part of a joint U.S. Department of Agriculture/U.S. Environmental Protection Agency national survey of the U.S. poultry supply conducted in 1997. The affected animals, which had been raised in the southern United States, represented approximately 5% of the national poultry production . All of these chickens and other animal food sources (i.e., farm-raised catfish), similarly contaminated, were fed a diet of animal feed containing ball clay as an anti-caking additive. The clay was mined in northwestern Mississippi within a geological formation referred to as the Mississippi Embayment. Individual raw and processed ball clay samples were analyzed for the presence of the 2,3,7,8-PCDDs/PCDFs. The average toxic equivalents (TEQs) for the raw and processed samples were 1513 and 996 ppt dry weight, respectively. Other mined clay-based products used in animal feeds revealed lower TEQs. All of the products exhibited either an absence of detectable concentrations of 2,3,7,8-PCDFs or concentrations 2-3 orders of magnitude lower than the PCDDs. The isomer distribution, specific isomer identification, and congener profile of the PCDDs in the clay were established and compared to known sources of dioxin contamination. Several unique features of this isomer distribution are characteristic of the clays and are distinguishable from those other known sources. These characteristic

  2. Integrating Health and Sustainability: The Higher Education Sector as a Timely Catalyst

    ERIC Educational Resources Information Center

    Orme, J.; Dooris, M.

    2010-01-01

    Higher education is an influential sector with enormous potential to impact positively on health and sustainability. The purpose of this paper was to explore its emergent role as a key setting for promoting health and sustainability and for addressing their challenges in an integrated and coherent way. Acknowledging both the relative narrowness of…

  3. Rural Education: A Field of Study Whose Time Has Come in Higher Education.

    ERIC Educational Resources Information Center

    Warner, Richard W., Jr.; Kale, Karen E.

    Although professional educators and public school decision makers have attempted to respond to increased educational demands and a broader spectrum of students, the education of rural youth is a neglected area both in higher education and in educational legislation. The record indicates that policy decisions and the resulting legislation have…

  4. The Effective Academic: A Handbook for Enhanced Academic Practice. The Times Higher Education Supplement.

    ERIC Educational Resources Information Center

    Ketteridge, Steve, Ed.; Marshall, Stephanie, Ed.; Fry, Heather, Ed.

    This handbook provides guidance about controlling and directing an academic career by suggesting systematic approaches to key areas of responsibility and activity. It explores management and leadership in higher education, developing and promoting research and teaching, and coping with the changing university environment. The chapters of part 1,…

  5. Challenges to Christian Higher Education at a Time of Increasing Emphasis on Research

    ERIC Educational Resources Information Center

    Hemmings, Brian; Hill, Doug

    2014-01-01

    In Australia, both Christian and non-Christian higher education institutions (HEIs) have experienced a rapidly changing external environment that is becoming more performance-driven, particularly in relation to faculty research. Academics working in Australian Christian HEIs often feel pressure to keep pace with their counterparts in non-Christian…

  6. Higher Education in a Dangerous Time: Will Technology Really Improve the University?

    ERIC Educational Resources Information Center

    Mahoney, John

    1998-01-01

    States that cost-control and efficiency initiatives will continue to be directed at higher education. Suggests that rather than focusing on technology it might be wiser to focus on attaining the highest standards in teaching, innovative learning opportunities, academic advising, and student-development services throughout the nation's colleges and…

  7. The Challenge and Promise of Catholic Higher Education for Our Time

    ERIC Educational Resources Information Center

    Jenkins, John I.

    2015-01-01

    Catholic colleges and universities face significant challenges in the present context of American higher education. Yet, there are opportunities to be found in the midst of this crisis when one carefully examines the intersections between the Catholic mission and objectives of an institution and current culture and academia. A return to the…

  8. Exposure and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in tree swallows (Tachycineta bicolor) nesting along the Woonasquatucket River, Rhode Island, USA

    USGS Publications Warehouse

    Custer, Christine M.; Custer, T.W.; Rosiu, C.J.; Melancon, M.J.; Bickham, J.W.; Matson, C.W.

    2005-01-01

    Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in tree swallows (Tachycineta bicolor) nesting along the Woonasquatucket River northwest of Providence (RI, USA) in 2000 and 2001 were some of the highest ever reported in avian tissues. Mean concentrations in eggs ranged from 300 to >1,000 pg/g wet weight at the two most contaminated ponds, Allendale and Lyman. Mean egg concentrations at Greystone, the upstream reference pond, were 12 and 29 pg/g. Positive accumulation rates and concentrations in diet samples from 12-day-old nestlings indicated that the contamination was accumulated locally. Concentrations in diet of between 71 and 219 pg/g wet weight were more than 6 and 18 times higher than concentrations considered safe for birds (10?12 pg/g). Hatching success was negatively associated with concentration of TCDD in eggs. Only about half the eggs hatched at Allendale compared with >77% at Greystone. The national average for hatching success in successful nests is 85%. No other contaminants, such as polychlorinated biphenyls and mercury, were present in any sample at concentrations known to affect avian reproduction. Three bioindicators, half-peak coefficient of geometric variation, ethoxyresorufin-O-dealkylase activity, and brain asymmetry were assessed relative to TCDD contamination.

  9. Exposure and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in tree swallows (Tachycineta bicolor) nesting along the Woonasquatucket River, Rhode Island, USA

    USGS Publications Warehouse

    Custer, Christine M.; Custer, T.W.; Rosiu, C.J.; Melancon, M.J.; Bickham, J.W.; Matson, C.W.

    2005-01-01

    Concentrations of 2,3,7,8 -tetrachlorodibenzo-p-dioxin (TCDD) in tree swallows (Tachycineta hicolor) nesting along the Woonasquatucket River northwest of Providence (RI, USA) in 2000 and 2001 were some of the highest ever reported in avian tissues. Mean concentrations in eggs ranged from 300 to > 1,000 pg/g wet weight at the two most contaminated ponds, Allendale and Lyman. Mean egg concentrations at Greystone, the upstream reference pond, were 12 and 29 pg/g. Positive accumulation rates and concentrations in diet samples from 12-day-old nestlings indicated that the contamination was accumulated locally. Concentrations in diet of between 71 and 219 pg/g wet weight were more than 6 and 18 times higher than concentrations considered safe for birds (10- 12 pg/g). Hatching success was negatively associated with concentration of TCDD in eggs. Only about half the eggs hatched at Allendale compared with >77% at Greystone. The national average for hatching success in successful nests is 85%. No other contaminants, such as polychlorinated biphenyls and mercury, were present in any sample at concentrations known to affect avian reproduction. Three bioindicators, half-peak coefficient of geometric variation, ethoxyresorufin-O-dealkylase activity, and brain asymmetry were assessed relative to TCDD contamination.

  10. Synthesis of 3-aryl-8-oxo-5,6,7,8-tetrahydroindolizines via a palladium-catalyzed arylation and heteroarylation.

    PubMed

    Gracia, Stéphanie; Cazorla, Clément; Métay, Estelle; Pellet-Rostaing, Stéphane; Lemaire, Marc

    2009-04-17

    A selective palladium-catalyzed arylation and heteroarylation of 8-oxo-5,6,7,8-tetrahydroindolizines has been developed. Mechanistic studies assume an electrophilic substitution pathway for this transformation. This method provides an efficient one-step synthesis of 3-aryl-8-oxo-5,6,7,8-tetrahydroindolizines.

  11. Time-harmonic elasticity with controllability and higher-order discretization methods

    NASA Astrophysics Data System (ADS)

    Mönkölä, Sanna; Heikkola, Erkki; Pennanen, Anssi; Rossi, Tuomo

    2008-05-01

    The time-harmonic solution of the linear elastic wave equation is needed for a variety of applications. The typical procedure for solving the time-harmonic elastic wave equation leads to difficulties solving large-scale indefinite linear systems. To avoid these difficulties, we consider the original time dependent equation with a method based on an exact controllability formulation. The main idea of this approach is to find initial conditions such that after one time-period, the solution and its time derivative coincide with the initial conditions. The wave equation is discretized in the space domain with spectral elements. The degrees of freedom associated with the basis functions are situated at the Gauss-Lobatto quadrature points of the elements, and the Gauss-Lobatto quadrature rule is used so that the mass matrix becomes diagonal. This method is combined with the second-order central finite difference or the fourth-order Runge-Kutta time discretization. As a consequence of these choices, only matrix-vector products are needed in time dependent simulation. This makes the controllability method computationally efficient.

  12. Integrating health and sustainability: the higher education sector as a timely catalyst.

    PubMed

    Orme, J; Dooris, M

    2010-06-01

    Higher education is an influential sector with enormous potential to impact positively on health and sustainability. The purpose of this paper was to explore its emergent role as a key setting for promoting health and sustainability and for addressing their challenges in an integrated and coherent way. Acknowledging both the relative narrowness of the environmental focus that has to date characterized and driven universities' work in relation to sustainability and the demonstrable value of adopting a whole-system approach, this paper will explore the concept of 'Healthy Universities' as a means of furthering debate and facilitating synergy between public health, sustainable development and climate change. Higher education represents one large-scale sector with a unique combination of roles that can be harnessed to focus and mobilize its education, knowledge exchange, research, corporate responsibility and future shaping agendas to achieve significant impacts in this area. It is the growing commitment to embedding health and well-being within the mainstream business of higher education coupled with the expectation that universities will act sustainably in all that they do that provides the perfect springboard to influence a process of 'co-ordinated action' to address climate change and impact positively on the integrated health and sustainability agenda.

  13. Effects of the 7-8-year cycle in daily mean air temperature as a cross-scale information transfer

    NASA Astrophysics Data System (ADS)

    Jajcay, Nikola; Hlinka, Jaroslav; Paluš, Milan

    2015-04-01

    Using a novel nonlinear time-series analysis method, an information transfer from larger to smaller scales of the air temperature variability has been observed in daily mean surface air temperature (SAT) data from European stations as the influence of the phase of slow oscillatory phenomena with periods around 6-11 years on amplitudes of the variability characterized by smaller temporal scales from a few months to 4-5 years [1]. The strongest effect is exerted by an oscillatory mode with the period close to 8 years and its influence can be seen in 1-2 °C differences of the conditional SAT means taken conditionally on the phase of the 8-year cycle. The size of this effect, however, changes in space and time. The changes in time are studied using sliding window technique, showing that the effect evolves in time, and during the last decades the effect is stronger and significant. Sliding window technique was used along with seasonal division of the data, and it has been found that the cycle is most pronounced in the winter season. Different types of surrogate data are applied in order to establish statistical significance and distinguish the effect of the 7-8-yr cycle from climate variability on shorter time scales. [1] M. Palus, Phys. Rev. Lett. 112 078702 (2014) This study is supported by the Ministry of Education, Youth and Sports of the Czech Republic within the Program KONTAKT II, Project No. LH14001.

  14. Configuration of the C(20) Epimer of 7,8-Dihydrobatrachotoxinin A

    PubMed Central

    Karle, Isabella L.

    1972-01-01

    7,8-Dihydrobatrachotoxinin A is an intermediate in the synthesis of batrachotoxin, the extremely potent venom from the Colombian frog Phyllobates aurotaenia. A crystal structure analysis by x-ray diffraction has confirmed that the intermediate is identical with the natural batrachotoxinin A except for the saturation of the C(7)-C(8) bond. There are seven asymmetric carbon atoms in the molecule. The cis A/B and C/D ring junctions cause the molecule to assume the characteristic shape of cardioactive steroids. A cage is formed from the A-ring, atom C(9), and the O atom that makes the ether linkage between C(3) and C(9). PMID:4507615

  15. Biomagnification of bioassay derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents

    USGS Publications Warehouse

    Jones, P.D.; Ankley, G.T.; Best, D. A.; Crawford, R.; DeGalan, N.; Giesy, J.P.; Kubiak, T.J.; Ludwig, J. P.; Newsted, J.L.; Tillitt, D. E.; Verbrugge, D.A.

    1993-01-01

    In recent years contamination of the Great Lakes ecosystem with planar chlorinated hydrocarbons (PCHs) has attracted considerable concern due to their known reproductive and teratogenic effects. The H4IIE bioassay has been standardized as a means of measuring the biological potency of a PCH mixture as 2,3,7,8-tetrachloro-p-dibenzodioxin equivalents (TCDD-EQ). Using this bioassay we have investigated the biomagnification of TCDD-EQ in a semi-closed ecosystem. The biomagnification of TCDD-EQ is demonstrated and results indicate that the food chain is the major pathway for TCDD-EQ through this ecosystem. The H4IIE assay system is demonstrated to be a viable integrative measure of the total concentration of TCDD-EQ in different trophic levels.

  16. Cancer Therapeutic Resistance: Progress and Perspectives (April 7-8, 2016 - Barcelona, Spain).

    PubMed

    Hutchinson, E; Pujana, M A; Arribas, J

    2016-06-01

    At the Cancer Therapeutic Resistance: Progress and Perspectives conference, in Barcelona, Spain, April 7-8, 2016, researchers, clinicians and students gathered to discuss our current understanding of intrinsic and acquired resistance of tumors to cancer therapies and to explore how to translate strategies to predict risk or overcome resistance to the clinic. The sessions covered a wide range of topics, including cancer omics, molecular classification, clinically relevant tumor models, biomarkers and novel therapeutic targets, and personalized medicine, with talks from many international experts in the field. This report highlights the main presentations that demonstrate the progress being made in predicting and identifying drug resistance in patients with cancer, personalized approaches to direct treatment and understanding the mechanisms involved. With better models of human cancer and powerful high-throughput screening techniques, translation to the clinic leading to tangible benefits for patients is attainable.

  17. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and long term immunologic memory.

    PubMed

    Sherr, David H

    2004-06-01

    The highlighted article by B. Paige Lawrence and Beth Vorderstrasse addresses an oft forgotten aspect of immunotoxicity, the effects of environmental toxins on immunologic memory. Here, the authors take a step towards filling that information gap by evaluating the effects of a prototypic environmental toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on memory responses to a real-world pathogen, influenza A virus, presented to an animal model in a physiologically relevant manner. Multiple outcomes are evaluated, the vast majority of which suggest important and long-term TCDD-induced changes in the immune system after both primary and secondary exposure to this pathogen. The implications of these studies with regard to the immuno-competence of TCDD-exposed individuals are far reaching.

  18. Gravity increase before the 2015 Mw 7.8 Nepal earthquake

    NASA Astrophysics Data System (ADS)

    Chen, Shi; Liu, Mian; Xing, Lelin; Xu, Weimin; Wang, Wuxing; Zhu, Yiqing; Li, Hui

    2016-01-01

    The 25 April 2015 Nepal earthquake (Mw 7.8) ruptured a segment of the Himalayan front fault zone. Four absolute gravimetric stations in southern Tibet, surveyed from 2010/2011 to 2013 and corrected for secular variations, recorded up to 22.40 ± 1.11 μGal/yr of gravity increase during this period. The gravity increase is distinct from the long-wavelength secular trends of gravity decrease over the Tibetan Plateau and may be related to interseismic mass change around the locked plate interface under the Himalayan-Tibetan Plateau. We modeled the source region as a disk of 580 km in diameter, which is consistent with the notion that much of the southern Tibetan crust is involved in storing strain energy that drives the Himalayan earthquakes. If validated in other regions, high-precision ground measurements of absolute gravity may provide a useful method for monitoring mass changes in the source regions of potential large earthquakes.

  19. Synthesis and biological studies of 4', 7, 8-trihydroxy-isoflavone metal complexes.

    PubMed

    Tang, Li-Jun; Chen, Xiang; Sun, Yu-Na; Ye, Jia; Lu, Jing; Han, Ying; Jiang, Xing; Cheng, Chan-Chan; He, Cheng-Cheng; Qiu, Pei-Hong; Li, Xiao-Kun

    2011-12-01

    A new series of complexes of a ligand 4', 7, 8-trihydroxy-isoflavone with transition metal (zinc, copper, manganese, nickel, cobalt) and selenium have been synthesized and characterized with the aid of elemental analysis, IR, electron ionization mass spectrum (EI-MS) and (1)H NMR spectrometric techniques. The compounds were evaluated for their in vitro antibacterial activities and antitumor properties. The metal complexes were found to be more active than the free ligand. Investigation on the interaction between the complexes and calf-thymus DNA (CT DNA) showed that the absorbance of CT DNA increased and the maximum peak (λ(max)=260 nm) red-shifted, while the intensity of fluorescence spectra of Epstein-Bart DNA (EB-DNA) gradually weakened, which indicated that all of these metal complexes tightly combined with CT DNA.

  20. Skin tumor initiating ability of benzo(a)pyrene 4,5- 7,5- and 7,8-diol-9,10-epoxides and 7,8-diol.

    PubMed

    Slaga, T J; Viaje, A; Betty, D L; Brachen, W; Buty, S G; Scribner, J D

    1976-11-01

    The skin tumor initiating abilities of both K-region and non-K-region epoxides of benzo(a)pyrene(BP) were determined in mice using a two-stage system of tumorigenesis. BP-4,5-epoxide and BP-7,8-dihydrodiol-9,10-epoxide (anti) were found to be weak tumor initiators whereas BP-7,8-epoxide had about a third of the activity as the parent hydrocarbon, BP. However, the 7,8-dihydrodiol of BP was found to be approximately as potent as BP suggesting that it may be a proximate carcinogen.

  1. Higher Dimensional Clayton–Oakes Models for Multivariate Failure Time Data

    PubMed Central

    Prentice, R. L.

    2016-01-01

    Summary The Clayton–Oakes bivariate failure time model is extended to dimensions m > 2 in a manner that allows unspecified marginal survivor functions for all dimensions less than m. Special cases that allow unspecified marginal survivor functions of dimension q with q < m, while making some provisions for dependencies of dimension greater than q, are also described. PMID:27738350

  2. Transformation or Decline? Using Tough Times to Create Higher-Performing Schools

    ERIC Educational Resources Information Center

    Miles, Karen Hawley

    2011-01-01

    Instead of doing less with less during these fiscally challenging times, school districts can seize the moment to usher in school transformation that will leave the schools, families, and communities better off. They could follow the lead of districts such as Baltimore City, Syracuse, and Charlotte-Mecklenburg to think outside traditional cost…

  3. Spanish Zimbardo Time Perspective Inventory Construction and Validity among Higher Education Students

    ERIC Educational Resources Information Center

    Usart, Mireia; Romero, Margarida

    2014-01-01

    Introduction: The study of "Time Orientation" (TO) has been focused on how to measure this construct and its effects on human behavior. Defined as a fundamental psychological variable, TO is multidimensional, sensible to cultural differences and age. Although its relation to learning, it deserves further study in the different Higher…

  4. Higher Prevalence of Left-Handedness in Twins? Not After Controlling Birth Time Confounders.

    PubMed

    Heikkilä, Kauko; Vuoksimaa, Eero; Saari-Kemppainen, Aulikki; Kaprio, Jaakko; Rose, Richard J; Haukka, Jari; Pitkäniemi, Janne; Iivanainen, Matti

    2015-10-01

    Pregnancy- and birth-related factors may have an effect on handedness. Compared with singletons, twins have a lower birth weight, shorter gestational age, and are at higher risk for birth complications. We tested whether the prevalence of left-handedness is higher among twins than singletons, and if so, whether that difference is fully explained by pregnancy and birth-related differences between twins and singletons. We analyzed Finnish population-based datasets; included were 8,786 twins and 5,892 singletons with information on birth weight (n = 12,381), Apgar scores (n = 11,129), and gestational age (n = 11,811). Two twin cohorts were involved: FinnTwin12 included twins born during 1983-1987, and FinnTwin16 included twins born during 1974-1979. We had two comparison groups of singletons: 4,101 individuals born during 1986-1988 and enrolled in the Helsinki Ultrasound Trial, and 1,791 individuals who were partners of FinnTwin16 twins. We used logistic regression models with writing hand as the outcome for comparison and evaluating effects of covariates. Left-handedness was more common in twins (9.67%) than in singletons (8.27%; p = .004). However, Apgar scores were associated with handedness, and after controlling for covariates, we found no difference in the prevalence of left-handedness between twins and singletons. Increased left-handedness among twins, often reported by others, was evident in our data, but only among our older twin cohorts, and that association disappeared after removing effects of perinatal covariates.

  5. Tensor-product preconditioners for higher-order space-time discontinuous Galerkin methods

    NASA Astrophysics Data System (ADS)

    Diosady, Laslo T.; Murman, Scott M.

    2017-02-01

    A space-time discontinuous-Galerkin spectral-element discretization is presented for direct numerical simulation of the compressible Navier-Stokes equations. An efficient solution technique based on a matrix-free Newton-Krylov method is developed in order to overcome the stiffness associated with high solution order. The use of tensor-product basis functions is key to maintaining efficiency at high-order. Efficient preconditioning methods are presented which can take advantage of the tensor-product formulation. A diagonalized Alternating-Direction-Implicit (ADI) scheme is extended to the space-time discontinuous Galerkin discretization. A new preconditioner for the compressible Euler/Navier-Stokes equations based on the fast-diagonalization method is also presented. Numerical results demonstrate the effectiveness of these preconditioners for the direct numerical simulation of subsonic turbulent flows.

  6. Higher-order hybrid implicit/explicit FDTD time-stepping

    NASA Astrophysics Data System (ADS)

    Tierens, W.

    2016-12-01

    Both partially implicit FDTD methods, and symplectic FDTD methods of high temporal accuracy (3rd or 4th order), are well documented in the literature. In this paper we combine them: we construct a conservative FDTD method which is fourth order accurate in time and is partially implicit. We show that the stability condition for this method depends exclusively on the explicit part, which makes it suitable for use in e.g. modelling wave propagation in plasmas.

  7. Anticancer activity of 7,8-dihydroxyflavone in melanoma cells via downregulation of α-MSH/cAMP/MITF pathway.

    PubMed

    Sim, Deok Yong; Sohng, Jae Kyung; Jung, Hye Jin

    2016-07-01

    Malignant melanoma is one of the most aggressive skin cancer and highly resistant to most conventional treatment. In the present study, we aimed to investigate the anticancer effects and mechanisms of action of 7,8-dihydroxyflavone (7,8-DHF), a monophenolic flavone, in melanoma cells. At concentrations not exhibiting cytotoxicity, 7,8-DHF potently inhibited growth and clonogenic survival of alpha-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. Furthermore, it significantly blocked migration and invasion of the metastatic melanoma cells. We also observed that 7,8-DHF exhibits anti-melanogenic activity through inhibition of tyrosinase activity in α-MSH-stimulating condition. Notably, the suppressive activities of 7,8-DHF on melanoma progression were associated with the downregulation of microphthalmia-associated transcription factor (MITF) and its main downstream transcription targets, including hypoxia-inducible factor 1α (HIF1α) and c-MET, by a decrease in cyclic adenosine monophosphate (cAMP) level. In addition, combination treatment with 7,8-DHF and resveratrol, a known therapeutic agent against melanoma, had greater anticancer activities and MITF inhibition than treatment with each single agent in α-MSH-treated B16F10 cells. Collectively, these findings may contribute to the potential application of 7,8-DHF in the prevention and treatment of malignant melanoma.

  8. 7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Zhang, Zhentao; Liu, Xia; Schroeder, Jason P; Chan, Chi-Bun; Song, Mingke; Yu, Shan Ping; Weinshenker, David; Ye, Keqiang

    2014-01-01

    Synaptic loss in the brain correlates well with disease severity in Alzheimer disease (AD). Deficits in brain-derived neurotrophic factor/tropomyosin-receptor-kinase B (TrkB) signaling contribute to the synaptic dysfunction of AD. We have recently identified 7,8-dihydroxyflavone (7,8-DHF) as a potent TrkB agonist that displays therapeutic efficacy toward various neurological diseases. Here we tested the effect of 7,8-DHF on synaptic function in an AD model both in vitro and in vivo. 7,8-DHF protected primary neurons from Aβ-induced toxicity and promoted dendrite branching and synaptogenesis. Chronic oral administration of 7,8-DHF activated TrkB signaling and prevented Aβ deposition in transgenic mice that coexpress five familial Alzheimer's disease mutations (5XFAD mice). Moreover, 7,8-DHF inhibited the loss of hippocampal synapses, restored synapse number and synaptic plasticity, and prevented memory deficits. These results suggest that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating AD. PMID:24022672

  9. The DnaJ OsDjA7/8 is essential for chloroplast development in rice (Oryza sativa).

    PubMed

    Zhu, Xiaobo; Liang, Sihui; Yin, Junjie; Yuan, Can; Wang, Jing; Li, Weitao; He, Min; Wang, Jichun; Chen, Weilan; Ma, Bingtian; Wang, Yuping; Qin, Peng; Li, Shigui; Chen, Xuewei

    2015-12-10

    DnaJ proteins belong to chaperones of Hsp40 family that ubiquitously participate in various cellular processes. Previous studies have shown chloroplast-targeted DnaJs are involved in the development of chloroplast in some plant species. However, little is known about the function of DnaJs in rice, one of the main staple crops. In this study, we characterized a type I DnaJ protein OsDjA7/8. We found that the gene OsDjA7/8 was expressed in all collected tissues, with a priority in the vigorous growth leaf. Subcellular localization revealed that the protein OsDjA7/8 was mainly distributed in chloroplast. Reduced expression of OsDjA7/8 in rice led to albino lethal at the seedling stage. Transmission electron microscopy observation showed that the chloroplast structures were abnormally developed in the plants silenced for OsDjA7/8. In addition, the transcriptional expression of the genes tightly associated with the development of chloroplast was deeply reduced in the plants silenced for OsDjA7/8. Collectively, our study reveals that OsDjA7/8 encodes a chloroplast-localized protein and is essential for chloroplast development and differentiation in rice.

  10. 7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

    PubMed Central

    Ma, Rui; Zhang, Jisheng; Liu, Xiaoyu; Yue, Shaoheng; Zhao, Qing

    2016-01-01

    Acute kidney injury (AKI) is a common syndrome which is strongly linked to high morbidity and mortality. Hypoxia is the leading cause of AKI and the proximal renal tubular cells are the most damaged part in the kidney during this period. It has been observed that 7,8-dihydroxyflavone (7,8-DHF) plays a protective role by acting on antiapoptosis and antioxidative stress. In this study we explored functions of 7,8-DHF in protecting human proximal tubular cell line HK-2 from hypoxia insults. We observed that treatment of 7,8-DHF could improve the viability of ischemic cell. Mechanistically, we found that 7,8-DHF could elevate the expression of cysteine-rich protein 61 (Cyr61), a protective immediate early gene in AKI. In addition, treatment of 7,8-DHF decreased CCAAT/enhancer-binding protein homologous protein (CHOP) expression, which is a marker protein during endoplasmic reticulum (ER) stress activation. Intriguingly, overexpression of Cyr61 significantly reduced CHOP expression. Taken together, our results provide novel insights into the possible protective role of 7,8-DHF by activating Cyr61 signaling and suppressing ER stress in hypoxic HK-2 cells which have potential clinical implications for the treatment of AKI. PMID:28116298

  11. Impact-induced muscle damage and urinary pterins in professional rugby: 7,8-dihydroneopterin oxidation by myoglobin.

    PubMed

    Lindsay, A; Healy, J; Mills, W; Lewis, J; Gill, N; Draper, N; Gieseg, S P

    2016-03-01

    Muscle damage caused through impacts in rugby union is known to increase oxidative stress and inflammation. Pterins have been used clinically as markers of oxidative stress, inflammation, and neurotransmitter synthesis. This study investigates the release of myoglobin from muscle tissue due to force-related impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin oxidation were examined in vitro via strong cation-exchange high-performance liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8-dihydroxanthopterin. Urine samples were collected from 25 professional rugby players pre and post four games and analyzed for myoglobin by enzyme-linked immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8-dihydroxanthopterin at concentrations at or above 10 μM and 50 μg/mL, respectively. All four games showed significant increases in myoglobin, neopterin, total neopterin, biopterin, and total biopterin, which correlated between each variable (P < 0.05). Myoglobin and iron facilitate 7,8-dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization of myoglobin due to muscle damage may contribute to oxidative stress and inflammation after rugby. Increased concentrations of biopterin and total biopterin may indicate production of nitric oxide and monoamine neurotransmitters in response to the physical stress.

  12. Fate of 3-tert-Butyl-4-hydroxyanisole, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8- hexamethylcyclopenta(g)-2-benzopyrane and chlorpyrifos in a Conventional Wastewater Treatement Plant

    NASA Astrophysics Data System (ADS)

    Thomas, S. M.; Bodour, A.; Inniss, E. C.; Murray, K. E.

    2007-12-01

    Emerging contaminants (ECs) are a major concern in the environment, particularly those found in waters. Wastewater treatment plants (WWTPs) play a key role in reducing the concentrations in the environment because compounds may be transformed under either aerobic or anaerobic conditions or may sorb to wastewater sludges and therefore be removed from waters. If these ECs are not contained or treated then effluent discharged from the WWTP and to a receiving stream may contain hazardous levels of these contaminants. Reported here is a study of the fate of three emerging contaminants (ECs): 3-tert-Butyl-4-hydroxyanisole (BHA), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyrane (HHCB) and chlorpyrifos. Experiments were conducted on a laboratory scale by emulating conditions of a conventional WWTP in San Antonio, TX. The goal of the research was to determine general characteristics for both sorption (to wastewater sludges) and degradation. The sorption experiments were performed by exposing the sludge to a variety of initial concentration of ECs for 24 hours. After exposure these three ECs were extracted and analyzed using gas chromatography followed by flame ionization detector (GC/FID). Sorption experiments indicated that HHCB and chlorpyrifos are more hydrophobic than BHA and, therefore, would be mostly contained in the sludges. The degradation rates for these ECs were also considered for both aerobic and anaerobic conditions using different bench-scale reactor setups for 21 days. The differences between the reactor setups included volume of reactor, amount of sludge, mode of supply of nutrients and acclimatization of sludge to the ECs. One sludge was first acclimated to EC concentrations and then used in the experiment. The acclimated reactor had reaction rate constants approximately double that of the non-acclimated sludge reactor setups and followed first order reaction kinetics. Aerobic degradation occurred more readily for all three compounds

  13. Higher-Pressure Ion Funnel Trap Interface for Orthogonal Time-of-Flight Mass Spectrometry

    PubMed Central

    Ibrahim, Yehia; Belov, Mikhail E.; Tolmachev, Aleksey V.; Prior, David C.; Smith, Richard D.

    2008-01-01

    A combined electrodynamic ion funnel and ion trap coupled to an orthogonal acceleration (oa)-time-of-flight mass spectrometer (oa-TOF MS) was developed and characterized. The ion trap was incorporated through the use of added terminal electrodynamic ion funnel electrodes enabling control over the axial DC gradient in the trap section. The ion trap operates efficiently at a pressure of 1 Torr, and measurements indicate a maximum charge capacity of ~3×107 charges. An order of magnitude increase in sensitivity was observed in the analysis of low concentration peptides mixtures with oa-TOF MS in the trapping mode as compared to the continuous regime. A signal increase in the trapping mode was accompanied by reduction in the background chemical noise, due to more efficient desolvation of e.g., solvent related clusters. Controlling the ion trap ejection time was found to result in efficient removal of singly charged species and improving signal-to-noise ratio (S/N) for the multiply charged analytes. PMID:17850113

  14. Modern U-Pb chronometry of meteorites: advancing to higher time resolution reveals new problems

    USGS Publications Warehouse

    Amelin, Y.; Connelly, J.; Zartman, R.E.; Chen, J.-H.; Gopel, C.; Neymark, L.A.

    2009-01-01

    In this paper, we evaluate the factors that influence the accuracy of lead (Pb)-isotopic ages of meteorites, and may possibly be responsible for inconsistencies between Pb-isotopic and extinct nuclide timescales of the early Solar System: instrumental mass fractionation and other possible analytical sources of error, presence of more than one component of non-radiogenic Pb, migration of ancient radiogenic Pb by diffusion and other mechanisms, possible heterogeneity of the isotopic composition of uranium (U), uncertainties in the decay constants of uranium isotopes, possible presence of "freshly synthesized" actinides with short half-life (e.g. 234U) in the early Solar System, possible initial disequilibrium in the uranium decay chains, and potential fractionation of radiogenic Pb isotopes and U isotopes caused by alpha-recoil and subsequent laboratory treatment. We review the use of 232Th/238U values to assist in making accurate interpretations of the U-Pb ages of meteorite components. We discuss recently published U-Pb dates of calcium-aluminum-rich inclusions (CAIs), and their apparent disagreement with the extinct nuclide dates, in the context of capability and common pitfalls in modern meteorite chronology. Finally, we discuss the requirements of meteorites that are intended to be used as the reference points in building a consistent time scale of the early Solar System, based on the combined use of the U-Pb system and extinct nuclide chronometers.

  15. A generative spike train model with time-structured higher order correlations.

    PubMed

    Trousdale, James; Hu, Yu; Shea-Brown, Eric; Josić, Krešimir

    2013-01-01

    Emerging technologies are revealing the spiking activity in ever larger neural ensembles. Frequently, this spiking is far from independent, with correlations in the spike times of different cells. Understanding how such correlations impact the dynamics and function of neural ensembles remains an important open problem. Here we describe a new, generative model for correlated spike trains that can exhibit many of the features observed in data. Extending prior work in mathematical finance, this generalized thinning and shift (GTaS) model creates marginally Poisson spike trains with diverse temporal correlation structures. We give several examples which highlight the model's flexibility and utility. For instance, we use it to examine how a neural network responds to highly structured patterns of inputs. We then show that the GTaS model is analytically tractable, and derive cumulant densities of all orders in terms of model parameters. The GTaS framework can therefore be an important tool in the experimental and theoretical exploration of neural dynamics.

  16. Accuracy of rate coding: When shorter time window and higher spontaneous activity help

    NASA Astrophysics Data System (ADS)

    Levakova, Marie; Tamborrino, Massimiliano; Kostal, Lubomir; Lansky, Petr

    2017-02-01

    It is widely accepted that neuronal firing rates contain a significant amount of information about the stimulus intensity. Nevertheless, theoretical studies on the coding accuracy inferred from the exact spike counting distributions are rare. We present an analysis based on the number of observed spikes assuming the stochastic perfect integrate-and-fire model with a change point, representing the stimulus onset, for which we calculate the corresponding Fisher information to investigate the accuracy of rate coding. We analyze the effect of changing the duration of the time window and the influence of several parameters of the model, in particular the level of the presynaptic spontaneous activity and the level of random fluctuation of the membrane potential, which can be interpreted as noise of the system. The results show that the Fisher information is nonmonotonic with respect to the length of the observation period. This counterintuitive result is caused by the discrete nature of the count of spikes. We observe also that the signal can be enhanced by noise, since the Fisher information is nonmonotonic with respect to the level of spontaneous activity and, in some cases, also with respect to the level of fluctuation of the membrane potential.

  17. A generative spike train model with time-structured higher order correlations

    PubMed Central

    Trousdale, James; Hu, Yu; Shea-Brown, Eric; Josić, Krešimir

    2013-01-01

    Emerging technologies are revealing the spiking activity in ever larger neural ensembles. Frequently, this spiking is far from independent, with correlations in the spike times of different cells. Understanding how such correlations impact the dynamics and function of neural ensembles remains an important open problem. Here we describe a new, generative model for correlated spike trains that can exhibit many of the features observed in data. Extending prior work in mathematical finance, this generalized thinning and shift (GTaS) model creates marginally Poisson spike trains with diverse temporal correlation structures. We give several examples which highlight the model's flexibility and utility. For instance, we use it to examine how a neural network responds to highly structured patterns of inputs. We then show that the GTaS model is analytically tractable, and derive cumulant densities of all orders in terms of model parameters. The GTaS framework can therefore be an important tool in the experimental and theoretical exploration of neural dynamics. PMID:23908626

  18. Space and time diversity in indoor wireless optical links achieving higher data rate

    NASA Astrophysics Data System (ADS)

    Alqudah, Yazan A.

    2013-02-01

    Multispot diffusing configuration (MSDC) in optical wireless links provide uniform optical power needed for multiaccess and spatial dependence that can be used to allow space diversity techniques over the link. The spatial channels are furnished in MSDC through utilizing multibeam transmitter that produces spatially confined diffusing spots, and a multibranch receiver with small enough branch field-of-view (FOV) to restrict the number of diffusing spots within its FOV. Here, we study different encoding techniques that use space and time diversity to reduce the bit error rate. An improved technique, constellation rotation, is proposed for pulse amplitude modulated (PAM) to increase the Euclidian distance between signal points, and thus reduce bit error. Our study shows that when a cap is placed on the amount of power allocated per channel, the performance of the improved 4-PAM using three spatial channels and soft binary decision provide the optimal performance. When the power allocated per user is restricted, the best performance is obtained through soft binary decision and by using symbols identified by their level and spatial channel to carry 2 bits per signal level-channel.

  19. Impact of the Headscarf Ban Policy on the Identity Development of Part-Time Unveilers in Turkish Higher Education

    ERIC Educational Resources Information Center

    Seggie, Fatma Nevra; Austin, Ann E.

    2010-01-01

    This qualitative study examines the impact of the Turkish higher education headscarf ban policy on the plural self-identities (i.e., as Turkish citizens, as Muslims, and as females) of part-time unveilers, female students who cover their hair in their private life but who remove the headscarf (or conceal it to appear unveiled) while at a Turkish…

  20. Utilizing Social Networks in Times of Crisis: Understanding, Exploring and Analyzing Critical Incident Management at Institutions of Higher Education

    ERIC Educational Resources Information Center

    Asselin, Martha Jo

    2012-01-01

    With the rising number of major crises on college campuses today (Security on Campus Inc., 2009), institutions of higher education can benefit from understanding of how social networks may be used in times of emergency. What is currently known about the usage of social networks is not integral to the current practices of crisis management that are…

  1. The Transition from Higher Education to Employment in Europe: The Analysis of the Time to Obtain the First Job

    ERIC Educational Resources Information Center

    Salas-Velasco, Manuel

    2007-01-01

    This paper investigates the determinants of the transition from higher education to work across Europe using various specifications of duration models and a one-time multi-country survey of university graduates from nine European countries. Results point to differences between the North and South of Europe in the difficulty of getting a first job.…

  2. Cooperative Weblog Learning in Higher Education: Its Facilitating Effects on Social Interaction, Time Lag, and Cognitive Load

    ERIC Educational Resources Information Center

    Huang, Tien-Chi; Huang, Yueh-Min; Yu, Fu-Yun

    2011-01-01

    This paper examines the effects of using weblog technologies to support cooperative learning in higher education. The study focused on the effects of features embedded in weblogs on social interactions, time lags, and cognitive loads. A quasi-experimental control-group research design was adopted. The participants were 115 undergraduates who were…

  3. Embryo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the wood duck (Aix sponsa)

    USGS Publications Warehouse

    Augspurger, T.P.; Tillitt, D.E.; Bursian, S.J.; Fitzgerald, S.D.; Hinton, D.E.; Di Giulio, R.T.

    2008-01-01

    We examined the sensitivity of the wood duck (Aix sponsa) embryo to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by injecting the toxicant into their eggs. Six groups of wood duck eggs (n = 35 to 211 per trial) were injected with 0 to 4600 pg TCDD/g egg between 2003 and 2005. Injections were made into yolk prior to incubation, and eggs were subsequently incubated and assessed weekly for mortality. Significant TCDD-induced mortality was not observed through day 25 (90% of incubation). Liver, heart, eye, and brain histology were generally unremarkable. Hepatic ethoxyresorufin-O-deethylase activity, a biomarker of dioxin-like compound exposure, was induced by 12-fold in the 4600 pg/g treatment relative to controls. The median lethal dose for chicken (Gallus domesticus) eggs we dosed identically to wood duck eggs was about 100 pg/g, similar to other assessments of chickens. Among dioxin-like compound embryo lethality data for 15 avian genera, the wood duck 4600 pg/g no-observed-effect level ranks near the middle. Because no higher doses were tested, wood ducks may be like other waterfowl (order Anseriformes), which are comparatively tolerant to embryo mortality from polychlorinated dibenzo-p-dioxins and dibenzofurans when exposed by egg injection. ?? 2008 US Government.

  4. Structure of the Meiyu Frontal System on 7-8 July 2007: Comparison between Cloud- resolving Simulations and Observations

    NASA Astrophysics Data System (ADS)

    Luo, Y.; Wang, Y.

    2008-12-01

    Meiyu frontal system that formed and moved over the Huai River basin of China on 7-8 July 2007 is investigated using weather radar observations, multiple satellite products, and surface meteorological and re- analysis data. Results from this analysis are used to evaluate cloud-resolving simulations with a focus on the vertical structure of hydrometeors. The convective systems consisted of generally west-east oriented leading convective lines with stratiform cloud regions trailing off to the north and east. Newer convection occurred on the western edge of the line. The convective centers progressed through a period of rapid growth, with echo tops penetrating to maximum heights of 16-km, then decreasing to height of 13-km, which corresponds to the height of the stratiform clouds with which the convective elements merged at the end of their lifetimes. The CONTROL simulation reasonably reproduced the spatial distribution of accumulated surface precipitation as well as the leading convective lines and trailing stratiform precipitation regions revealed by the observations. However, compared to the observations, the simulated convective cells are bigger and more intense extending higher into the troposphere while the stratiform regions are narrower. Significant differences are revealed between the vertical structure of the observed and simulated hydrometeors. Possible reasons for this discrepancy are presented. Sensitivity experiments are conducted to explore the impacts of microphysical and boundary layer processes on the simulated hydrometeor structure.

  5. Growth and characterization of 7,7,8,8-tetracyano-quinodimethane crystals on chemical vapor deposition graphene

    NASA Astrophysics Data System (ADS)

    Black, Andrés; Jiménez, Fernando; Bernardo-Gavito, Ramón; Casado, Santiago; Granados, Daniel; Vázquez de Parga, Amadeo L.

    2016-11-01

    Chemical functionalization of graphene could pave the way for favorably modifying its already remarkable properties. Organic molecules have been utilized to this end as a way to alter graphene's structural, chemical, electrical, optical and even magnetic properties. One such promising organic molecule is 7,7,8,8-tetracyano-quinodimethane (TCNQ), a strong electron acceptor which has been shown to be an effective p-dopant of graphene. This study explores the thermal evaporation of TCNQ onto graphene transferred onto SiO2/Si substrates. Using two different home-made thermal evaporators, a wide range of TCNQ growth regimes are explored, from thin films to bulk crystals. The resulting graphene/TCNQ structure is characterized via optical microscopy, Raman spectroscopy and atomic force microscopy (AFM). Films are found to be comprised of TCNQ and the oxidized product of TCNQ, α,α-dicyano-p-toluoylcyanide (DCTC), which confirms the electron charge transfer from graphene to the TCNQ films. AFM measurements of these films show that after forming a rather smooth layer covering the graphene surface, small clusters start to form. For higher TCNQ coverage, the clusters agglomerate, becoming quite large in size and forming ripples or wrinkles across the surface.

  6. Ionospheric disturbances triggered by the 25 April, 2015 M7.8 Gorkha earthquake, Nepal: Constraints from GPS TEC measurements

    NASA Astrophysics Data System (ADS)

    Catherine, J. K.; Uma Maheshwari, D.; Gahalaut, V. K.; Roy, P. N. S.; Khan, P. K.; Puviarasan, N.

    2017-01-01

    The ionosphere response to the April 11, 2015 (Mw 7.8) Gorkha earthquake, occurring in the Himalayan arc, is analysed using GPS Total Electron Content (TEC) measurements, from GPS sites in Nepal and India, situated both close to and far from the epicentre. In the near field, the Coseismic Ionospheric disturbance (CID) following the earthquake rupture propagation arrive east of the epicentre, within 5-7 min with a propagation velocity of 980 m/s, equal to the speed of the shock acoustic waves at the ionospheric heights, and on to the west with a reduced speed of 650 m/s, within 8-11 min, after the earthquake occurrence. The phenomenon of CID splitting into two modes, east and west of the epicentre is observed. In the far-field region, up to epicentral distances of 2200 km, Rayleigh wave induced ionospheric disturbance are recorded with a propagation speed of 2.6 km/s. Higher TEC amplitude of 0.2-1.5 TECU is observed east of the epicentre compared to the west with 0.1-0.3 TECU. The characteristics of this dip-slip earthquake are well projected in the TEC waveforms. The ambient magnetic field in the mid-latitudes prohibited the propagation of ionospheric disturbance in the northward direction. In the present study the observed primary CID is essentially in congruence with the rupture propagation of the earthquake in E-SE direction.

  7. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on development of anuran amphibians

    SciTech Connect

    Jung, R.E.; Walker, M.K.

    1997-02-01

    The authors exposed anuran eggs and tadpoles to vehicle control (0.7% acetone) or waterborne [{sup 3}H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h and subsequently raised them in clean water. Neither American toads nor green frogs exhibited TCDD-related mortality, but leopard frogs showed significantly increased mortality over controls. Eggs and tadpoles eliminated TCDD relatively quickly compared with published data for other vertebrates, with t{sub {1/2}} of 1 to 5 d (American toad), 2 to 7 d (leopard frog), and 4 to 6 d (green frog). Elimination rates were slowest for tadpoles fed nothing, fastest for those fed a low-fat diet, and intermediate for those fed a high-fat diet. Although not significant, American toads exposed to {ge}0.03 {micro}g TCDD/L appeared to metamorphose earlier, and those exposed to higher TCDD treatments appeared to metamorphose at a larger body mass than controls. Comparisons of these results with studies of fish early life stages suggest that anuran eggs and tadpoles eliminate TCDD more rapidly and are 100- to 1,000-fold less sensitive to its deleterious effects during development. These differences may be related to differences in metabolic rate, patterns of lipid storage and utilization, and aryl hydrocarbon receptor binding and signal transduction.

  8. Reading and writing performances of children 7-8 years of age with developmental coordination disorder in Taiwan.

    PubMed

    Cheng, Hsiang-Chun; Chen, Jenn-Yeu; Tsai, Chia-Liang; Shen, Miau-Lin; Cherng, Rong-Ju

    2011-01-01

    Developmental coordination disorder (DCD) refers to a delay in motor development that does not have any known medical cause. Studies conducted in English speaking societies have found that children with DCD display a higher co-occurrence rate of learning difficulties (e.g., problems in reading and writing) than typically developing (TD) children. The present study examined the reading and writing performance of school-aged children with DCD and TD children in Taiwan to determine whether reading and writing difficulties also co-occur with DCD in a non-English speaking society. The Chinese Reading Achievement Test and the Basic Reading and Writing Test were administered to 37 children with DCD (7.8 ± 0.6 years) and 93 TD children (8.0 ± 0.7 years). Children with DCD had significantly lower writing composite scores than TD children on the Basic Reading and Writing Test (105.9 ± 20.0 vs. 114.4 ± 19.9). However, there were no significant differences between children with DCD and TD children in their scores on the Chinese Reading Achievement Test and in their reading composite scores on the Basic Reading and Writing Test. These results contrasted interestingly with those obtained from English-speaking children: English-speaking DCD children showed poorer reading and poorer writing than English-speaking TD children. The possibility that the logographic nature of the Chinese script might have protected the DCD children against additional reading difficulty is discussed.

  9. 7,8-dihydroxyflavone facilitates the action exercise to restore plasticity and functionality: Implications for early brain trauma recovery.

    PubMed

    Krishna, Gokul; Agrawal, Rahul; Zhuang, Yumei; Ying, Zhe; Paydar, Afshin; Harris, Neil G; Royes, Luiz Fernando F; Gomez-Pinilla, Fernando

    2017-03-14

    Metabolic dysfunction accompanying traumatic brain injury (TBI) severely impairs the ability of injured neurons to comply with functional demands. This limits the success of rehabilitative strategies by compromising brain plasticity and function, and highlights the need for early interventions to promote energy homeostasis. We sought to examine whether the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) normalizes brain energy deficits and restablishes more normal patterns of functional connectivity, while enhancing the effects of exercise during post-TBI period. Moderate fluid percussion injury (FPI) was performed and 7,8-DHF (5mg/kg, i.p.) was administered in animals subjected to FPI that either had access to voluntary wheel running for 7days after injury or were sedentary. Compared to sham-injured controls, TBI resulted in reduced hippocampal activation of the BDNF receptor TrkB and associated CREB, reduced levels of plasticity markers GAP-43 and Syn I, as well as impaired memory as indicated by the Barnes maze task. While 7,8-DHF treatment and exercise individually mitigated TBI-induced effects, administration of 7,8-DHF concurrently with exercise facilitated memory performance and augmented levels of markers of cell energy metabolism viz., PGC-1α, COII and AMPK. In parallel to these findings, resting-state functional MRI (fMRI) acquired at 2weeks after injury showed that 7,8-DHF with exercise enhanced hippocampal functional connectivity, and suggests 7,8-DHF and exercise to promote increases in functional connectivity. Together, these findings indicate that post-injury 7,8-DHF treatment promotes enhanced levels of cell metabolism, synaptic plasticity in combination with exercise increases in brain circuit function that facilitates greater physical rehabilitation after TBI.

  10. Oxidative stress in lake sturgeon orally exposed to 2,3,7,8-tetrachlorodibenzofuran

    SciTech Connect

    Palace, V.P.; Dick, T.A.; Brown, S.B.; Baron, C.L.; Klaverkamp, J.F. |

    1994-12-31

    Juvenile lake sturgeon were orally dosed with gelatin containing nominal concentrations of 0, 0.16 or 1.6 ng 2,3,7,8-tetrachlorodibenzofuran (TCDF)/Kg fish weight. Liver, kidney and blood were collected 10 and 27 days after exposure. Phase 1 (mixed function oxidase MFO) and Phase 2 (glucuronyltransferase) enzyme activities were determined in liver. In addition, concentrations of nonenzymatic (ascorbic acid, tocopherol, retinoids) and enzymatic (superoxide dismutase, catalase, glutathione peroxidase) antioxidant parameters were quantified in liver and kidney. TCDF concentrations were elevated in liver and kidney of both dose groups at 10 and 27 days. However, lower tissue concentrations of TCDF at 27 days compared with 10 day exposures, as well as the presence of polar metabolites in bile, suggest rapid metabolism and clearance of the contaminant. Phase 1 and Phase 2 enzyme activities were induced in a dose dependent manner with activities at the two sample periods reflecting the different TCDF concentrations. Indicators of oxidative stress responded similarly.

  11. Kinematic and dynamic rupture process of the 2015 Nepal Mw 7.8 earthquake

    NASA Astrophysics Data System (ADS)

    Yin, J.; Yao, H.; Yang, H.

    2015-12-01

    On April 25 2015 a devastating Mw 7.8 earthquake occurred in Nepal and killed about 9000 people. This event is a typical low dip angle thrust event due to the collision and convergence between the Indian and Eurasian plate in the Himalayan arc since the last 1934 Mw 8.1 event. With the help of modern geophysical instrumental observation, such as seismic wave recordings, GPS and InSAR, the rupture process of this event can be well investigated. We use compressive sensing (CS) method to invert the coseismic radiation of this event in different frequency bands. Our CS results indicate an east-southeastward unilateral rupture process with frequency-dependent properties similar to that in oceanic subduction zone. This frequency-dependence and the seimogenic mechanism of this event are derived from the down-dip varied frictional properties in the Main Himalayan thrust (MHT). In the meanwhile, various observations indicate that the rupture of this event does not reach the ground surface and the shallow stick-slip portion of MHT is still locked, this is different from the 2008 Wenchuan event. To investigate why the rupture stops and does not reach the ground surface, we use numerical method to simulate the influence of high ground topography and fault geometry on the propagation of the rupture. Through combining the results from geophysical observation and numerical simulation, we can better understand the regional tectonic and estimate the potential seismic hazard in the active Himalayan arc.

  12. Elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxine in goat milk.

    PubMed

    Arstila, A U; Reggiani, G; Sorvari, T E; Räisänen, S; Wipf, H K

    1981-11-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxine (TCDD) 200 ng/day, was given orally to 7 goats for 2 months, followed by an elimination period of 1 month. Then a daily dose of 400 ng TCDD was given for 1 month to the same animals. Two animals were killed and the rest of the animals were observed for several months. The excretion of TCDD in milk was studied by glass capillary gas fragmentography, where the minimal detectable concentration was below 5 ppt. After the first feeding the concentration of TCDD in milk achieved a maximum of 20.8 +/- 6.6 ppt while a similar value of 19.3 +/- 6.6 ppt was observed after the second feeding. After this period, the concentration of TCDD decreased slowly with values, after 18 weeks, of 4, 2 +/-, 3 and 6 ppt. The concentration of TCDD in the liver in the two animals killed was 1039.0 and 898.0 ppt. There were no differences in clinical observations or blood and urine analyses when experimental animals were compared with controls.

  13. Gas-phase tropospheric chemistry of 2,3,7,8-tetrafuorinated dibenzo-p-dioxin.

    PubMed

    Zhang, Chenxi; Sun, Xiaomin

    2014-01-15

    Growing attention has been devoted to understanding the formation and destruction of polyfluorinated dibenzo-p-dioxins (PFDDs). High-accuracy molecular orbital calculations have been performed to investigate the tropospheric oxidation reaction of 2,3,7,8-tetrafuorinated dibenzo-p-dioxin (TFDD) initiated by OH radical, NO3 radical and O3. The rate constant of TFDD reaction triggered by the OH radical, NO3 radical and O3 is about 2.30 × 10(-11)cm(3) molecule(-l) s(-l), 3.18 × 10(-13)cm(3) molecule(-l) s(-l), and 3.30 × 10(-19)cm(3) molecule(-l) s(-l), respectively. OH radical is the major gas phase tropospheric sink for TFDD. Once TFDD-OH intermediates are produced in the initial reactions, they can react with tropospheric O2 subsequently to generate peroxy radical isomers. The TFDD-OH-O2 can further react with tropospheric NO via isomerization or combination, resulting that the dioxin ring will be ruptured completely. This study can serve as a template for tropospheric degradation of the gaseous PFDDs, which is beneficial for assessing their tropospheric behaviors.

  14. Interference between oculomotor and postural tasks in 7-8-year-old children and adults.

    PubMed

    Legrand, Agathe; Doré Mazars, Karine; Lemoine, Christelle; Nougier, Vincent; Olivier, Isabelle

    2016-06-01

    Several studies in adults having observed the effect of eye movements on postural control provided contradictory results. In the present study, we explored the effect of various oculomotor tasks on postural control and the effect of different postural tasks on eye movements in eleven children (7.8 ± 0.5 years) and nine adults (30.4 ± 6.3 years). To vary the difficulty of the oculomotor task, three conditions were tested: fixation, prosaccades (reactive saccades made toward the target) and antisaccades (voluntary saccades made in the direction opposite to the visual target). To vary the difficulty of postural control, two postural tasks were tested: Standard Romberg (SR) and Tandem Romberg (TR). Postural difficulty did not affect oculomotor behavior, except by lengthening adults' latencies in the prosaccade task. For both groups, postural control was altered in the antisaccade task as compared to fixation and prosaccade tasks. Moreover, a ceiling effect was found in the more complex postural task. This study highlighted a cortical interference between oculomotor and postural control systems.

  15. Frequency analysis of the 7-8 December 2010 extreme precipitation in the Panama Canal Watershed

    NASA Astrophysics Data System (ADS)

    Shamir, Eylon; Georgakakos, Konstantine P.; Murphy, Michael J.

    2013-02-01

    SummaryThe 7-8 December 2010 rainfall event in Panama produced record rainfall and streamflow that are about twice as much as for the previously observed large event in record. In this study we ask whether before the occurrence of this rainfall event, a return period estimate using the historical record and the commonly used statistical asymptotic distributions of extreme values could have indicated that such an event is probable. We examined the daily and 24-h mean areal rainfall over the entire Panama Canal Watershed with the Generalized Extreme Value, Gumbel, and Generalized Pareto distributions using the maximum likelihood approach for the parameter and uncertainty bounds estimation. We found that the solutions that maximized the log likelihood for these three distributions yield return period estimates that are larger than 2000 years. These return periods imply that the 2010 rainfall event was practically unforeseen. It is only the careful implementation of these distributions with full uncertainty analysis to define confidence intervals that yields estimates of return periods with substantial probabilities for such an event to occur. The GEV was found to be the most adequate distribution for this analysis, and the commonly-used Gumbel distribution, although indicated a good fit to the annual maxima series, attributed an extremely low probability for the occurrence of this event.

  16. Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects.

    PubMed Central

    Geusau, A; Abraham, K; Geissler, K; Sator, M O; Stingl, G; Tschachler, E

    2001-01-01

    A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication. PMID:11564625

  17. 8-Oxo-7,8-dihydroguanine: links to gene expression, aging, and defense against oxidative stress.

    PubMed

    Radak, Zsolt; Boldogh, Istvan

    2010-08-15

    The one-electron oxidation product of guanine, 8-oxo-7,8-dihydroguanine (8-oxoG), is an abundant lesion in genomic, mitochondrial, and telomeric DNA and RNA. It is considered to be a marker of oxidative stress that preferentially accumulates at the 5' end of guanine strings in the DNA helix, in guanine quadruplexes, and in RNA molecules. 8-OxoG has a lower oxidation potential compared to guanine; thus it is susceptible to oxidation/reduction and, along with its redox products, is traditionally considered to be a major mutagenic DNA base lesion. It does not change the architecture of the DNA double helix and it is specifically recognized and excised by 8-oxoguanine DNA glycosylase (OGG1) during the DNA base excision repair pathway. OGG1 null animals accumulate excess levels of 8-oxoG in their genome, yet they do not have shorter life span nor do they exhibit severe pathological symptoms including tumor formation. In fact they are increasingly resistant to inflammation. Here we address the rarely considered significance of 8-oxoG, such as its optimal levels in DNA and RNA under a given condition, essentiality for normal cellular physiology, evolutionary role, and ability to soften the effects of oxidative stress in DNA, and the harmful consequences of its repair, as well as its importance in transcriptional initiation and chromatin relaxation.

  18. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY ...

    EPA Pesticide Factsheets

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other known factors. owever, there exist animal cancer data indicating that TCDD can act as a tumor-promoting compound. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites. These observations in toto characterize TCDD as a complete carcinogen, which by definition encompasses both initiation and promotion carcinogenic activities. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites

  19. O-Methylated Metabolite of 7,8-Dihydroxyflavone Activates TrkB Receptor and Displays Antidepressant Activity

    PubMed Central

    Liu, Xia; Qi, Qi; Xiao, Ge; Li, Jingyu; Luo, Hongbo R.; Ye, Keqiang

    2016-01-01

    7,8-Dihydroxyflavone (7,8-DHF) acts as a TrkB receptor-specific agonist. It mimics the physiological actions of brain-derived neurotrophic factor (BDNF) and demonstrates remarkable therapeutic efficacy in animal models of various neurological diseases. Nonetheless, its in vivo pharmacokinetic profiles and metabolism remain unclear. Here we report that 7,8-DHF and its O-methylated metabolites distribute in mouse brain after oral administration. Both hydroxy groups can be mono-methylated, and the mono-methylated metabolites activate TrkB in vitro and in vivo. Blocking methylation, using COMT inhibitors, diminishes the agonistic effect of TrkB activation by 7,8-DHF or 4′-dimethylamino-7,8-DHF, supporting the contribution of the methylated metabolite to TrkB activation in mouse brain. Moreover, we have synthesized several methylated metabolite derivatives, and they also potently activate the TrkB receptor and reduce immobility in both forced swim test and tail suspension test, indicating that these methylated metabolites may possess antidepressant activity. Hence, our data demonstrate that 7,8-DHF is orally bioavailable and can penetrate the brain-blood barrier. The O-methylated metabolites are implicated in TrkB receptor activation in the brain. PMID:23445871

  20. Importance of Vibronic Effects in the UV-Vis Spectrum of the 7,7,8,8-Tetracyanoquinodimethane Anion.

    PubMed

    Tapavicza, Enrico; Furche, Filipp; Sundholm, Dage

    2016-10-11

    We present a computational method for simulating vibronic absorption spectra in the ultraviolet-visible (UV-vis) range and apply it to the 7,7,8,8-tetracyanoquinodimethane anion (TCNQ(-)), which has been used as a ligand in black absorbers. Gaussian broadening of vertical electronic excitation energies of TCNQ(-) from linear-response time-dependent density functional theory produces only one band, which is qualitatively incorrect. Thus, the harmonic vibrational modes of the two lowest doublet states were computed, and the vibronic UV-vis spectrum was simulated using the displaced harmonic oscillator approximation, the frequency-shifted harmonic oscillator approximation, and the full Duschinsky formalism. An efficient real-time generating function method was implemented to avoid the exponential complexity of conventional Franck-Condon approaches to vibronic spectra. The obtained UV-vis spectra for TCNQ(-) agree well with experiment; the Duschinsky rotation is found to have only a minor effect on the spectrum. Born-Oppenheimer molecular dynamics simulations combined with calculations of the electronic excitation energies for a large number of molecular structures were also used for simulating the UV-vis spectrum. The Born-Oppenheimer molecular dynamics simulations yield a broadening of the energetically lowest peak in the absorption spectrum, but additional vibrational bands present in the experimental and simulated quantum harmonic oscillator spectra are not observed in the molecular dynamics simulations. Our results underline the importance of vibronic effects for the UV-vis spectrum of TCNQ(-), and they establish an efficient method for obtaining vibronic spectra using a combination of linear-response time-dependent density functional theory and a real-time generating function approach.

  1. Carbon and nitrogen speciation in nitrogen-rich C-O-H-N fluids at 5.5-7.8 GPa

    NASA Astrophysics Data System (ADS)

    Sokol, Alexander G.; Palyanov, Yury N.; Tomilenko, Anatoly A.; Bul'bak, Taras A.; Palyanova, Galina A.

    2017-02-01

    Carbon and nitrogen speciation has been studied in high-pressure experiments in the C-O-H-N and C-O-H-N-Fe3C systems at 5.5 to 7.8 GPa and 1100 to 1500 °C using a split-sphere multi-anvil apparatus. Oxygen fugacity in the samples was either buffered by the Mo-MoO2 (MMO) and Fe-FeO (IW) equilibria using a double-capsule technique or left unbuffered. fO2 varied from 2 log units below to +4 log units above the iron-wüstite oxygen buffer (IW) depending on water contents in the charges and buffering. Ultra-reduced fluids contained NH3 as the dominant species, but its concentration was slightly lower, while CH4 was higher at higher temperatures. As oxygen fugacity and temperature increased to fO2 0.7 log units above IW and T ≥ 1400 °C, N2 became the predominant nitrogen species; the dominance among carbon species changed from CH4 and C2-C5 alkanes to oxygenated hydrocarbons and higher alkanes. It has been found out for the first time that the N2-rich fluid lacks methane at fO2 4 log units above IW but may bear a few percent of C2H6, C3H8, and C15-C18 alkanes and within one percent of alcohols, aldehydes, ketones, carboxylic acids, and furans. Thus, the NH3 enrichment of fluids and the nitrogen storage capacity of silicates at depths ∼200 km are expected to be the greatest in cold (1100-1200 °C) and reduced continental lithospheric mantle. In a hotter lithosphere of ∼1400 °C, the concentrations of NH3 and N2 in fluids are similar, and the nitrogen storage capacity of silicates should be relatively low. The stability of some higher alkanes and oxygenated hydrocarbons in nitrogen-rich fluids near the enstatite-magnesite-olivine-diamond/graphite (EMOG/D) equilibrium suggest that these carbon species, together with N2, can survive at the redox barrier, where silicate or silicate-carbonate melts capture them and entrain to shallow mantle.

  2. Broadband simulations for Mw 7.8 southern san andreas earthquakes: Ground motion sensitivity to rupture speed

    USGS Publications Warehouse

    Graves, R.W.; Aagaard, B.T.; Hudnut, K.W.; Star, L.M.; Stewart, J.P.; Jordan, T.H.

    2008-01-01

    Using the high-performance computing resources of the Southern California Earthquake Center, we simulate broadband (0-10 Hz) ground motions for three Mw 7.8 rupture scenarios of the southern San Andreas fault. The scenarios incorporate a kinematic rupture description with the average rupture speed along the large slip portions of the fault set at 0.96, 0.89, and 0.84 times the local shear wave velocity. Consistent with previous simulations, a southern hypocenter efficiently channels energy into the Los Angeles region along the string of basins south of the San Gabriel Mountains. However, we find the basin ground motion levels are quite sensitive to the prescribed rupture speed, with peak ground velocities at some sites varying by over a factor of two for variations in average rupture speed of about 15%. These results have important implications for estimating seismic hazards in Southern California and emphasize the need for improved understanding of earthquake rupture processes. Copyright 2008 by the American Geophysical Union.

  3. The ShakeOut scenario: A hypothetical Mw7.8 earthquake on the Southern San Andreas Fault

    USGS Publications Warehouse

    Porter, K.; Jones, L.; Cox, D.; Goltz, J.; Hudnut, K.; Mileti, D.; Perry, S.; Ponti, D.; Reichle, M.; Rose, A.Z.; Scawthorn, C.R.; Seligson, H.A.; Shoaf, K.I.; Treiman, J.; Wein, A.

    2011-01-01

    In 2008, an earthquake-planning scenario document was released by the U.S. Geological Survey (USGS) and California Geological Survey that hypothesizes the occurrence and effects of a Mw7.8 earthquake on the southern San Andreas Fault. It was created by more than 300 scientists and engineers. Fault offsets reach 13 m and up to 8 m at lifeline crossings. Physics-based modeling was used to generate maps of shaking intensity, with peak ground velocities of 3 m/sec near the fault and exceeding 0.5 m/sec over 10,000 km2. A custom HAZUS??MH analysis and 18 special studies were performed to characterize the effects of the earthquake on the built environment. The scenario posits 1,800 deaths and 53,000 injuries requiring emergency room care. Approximately 1,600 fires are ignited, resulting in the destruction of 200 million square feet of the building stock, the equivalent of 133,000 single-family homes. Fire contributes $87 billion in property and business interruption loss, out of the total $191 billion in economic loss, with most of the rest coming from shakerelated building and content damage ($46 billion) and business interruption loss from water outages ($24 billion). Emergency response activities are depicted in detail, in an innovative grid showing activities versus time, a new format introduced in this study. ?? 2011, Earthquake Engineering Research Institute.

  4. Toxicity and bioaccumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by Chironomus tentans and Lumbriculus variegatus

    SciTech Connect

    West, C.W.; Ankley, G.T.; Elonen, G.E.; Phipps, G.W.; Fernandez, J.D.; Libal, J.J.; Nessa, D.

    1994-12-31

    Invertebrate exposure to 2,3,7,8-TCDD is important, not necessarily because of their sensitivity (which appears to be less than that of fish) , but as a vector from chemical reservoirs in sediments, through the food chain, to sensitive species. Chironomus tentans and Lumbriculus variegatus are not only vectors for TCDD to fish species, but C. tentans may also be a direct vector to avian species which feed upon emergent insects. For this reason determination of the kinetics of TCDD uptake by invertebrates is important, especially for those with short life spans such as midges, or those that reproduce as rapidly as oligochaetes. In these experiments, these two species were fed contaminated food at three different TCDD levels spanning three orders of magnitude. Tissue residue levels were measured over a time period which included several different life stages and points in the reproductive cycle of the two species and uptake and deputation rates determined. As expected, no significant impacts of TCDD on growth, reproduction or biomass of the invertebrates were observed. From this information predictions can be made on bioaccumulation of TCDD from differing levels of contamination, and potential food chain transfer of the compound to more sensitive species.

  5. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation.

    PubMed

    Peltier, Morgan R; Arita, Yuko; Klimova, Natalia G; Gurzenda, Ellen M; Koo, Hchi-Chi; Murthy, Amitasrigowri; Lerner, Veronica; Hanna, Nazeeh

    2013-06-01

    Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can increase the risk of preterm birth in the offspring. How TCDD may modify placental immunity to ascending infections is unclear. Therefore, we studied the effects of TCDD treatment on basal and Escherichia coli-stimulated cytokine production by placental explants. Cultures of second-trimester placentas were treated with up to 40 nM TCDD for 72 h and then stimulated with 10(7)CFU/ml E. coli for an additional 24h. Concentrations of cytokines and PGE2 were measured in conditioned medium by immunoassay. TCDD exposure increased mRNA levels of IL-1β by unstimulated cultures, but no effects on protein levels of this cytokine were detected. TNF-α production was unaffected by TCDD for unstimulated cultures, but pre-treatment with 40 nM TCDD significantly increased E. coli-stimulated TNF-α production. Both basal and bacteria-stimulated PGE2 and COX-2 gene expression were enhanced by TCDD pretreatment. In contrast, production of the anti-inflammatory cytokine, IL-10, was reduced by TCDD pretreatment for both unstimulated and E. coli-stimulated cultures. No effect of TCDD on the viability of the cultures was detected. These results suggest that TCDD exposure may shift immunity to enhance a proinflammatory phenotype at the maternal-fetal interface that could increase the risk of infection-mediated preterm birth.

  6. Biochemical identification of a hydroperoxide derivative of the free 8-oxo-7,8-dihydroguanine base

    PubMed Central

    Hajas, Gyorgy; Bacsi, Attila; Aguilerra-Aguirre, Leopoldo; German, Peter; Radak, Zsolt; Sur, Sanjiv; Hazra, Tapas K.; Boldogh, Istvan

    2011-01-01

    8-Oxo-7,8-dihydroguanine is one the most abundant base lesions in pro- and eukaryotic DNA. In mammalian cells, it is excised by the 8-oxoguanine DNA glycosylases (OGG1) during DNA base excision repair, and the generated free 8-oxoG base (8-oxoG) is one of the DNA-derived biomarkers of oxidative stress in biological samples. The modification of 8-oxoG in the context of nucleoside and DNA has been the subject of many studies; however, the oxidative transformation of the free 8-oxoG base has not been described. By using biochemical and cell biological assays, we showed that in the presence of molecular oxygen, the free 8-oxoG base transformed to a highly reactive hydroperoxide (8-oxoG*). Specifically, 8-oxoG* oxidizes Amplex Red to resorufin, H2DCF to DCF, Fe2+ to Fe3+, and GSH to GSSG. This property of 8-oxoG* was diminished by treatment with catalase, glutathione peroxidase, but not superoxide dismutase. 8-oxoG* formation was prevented by reducing agents or nitrogen atmosphere. Its addition to H2DCF-DA-loaded cells rapidly increased intracellular DCF fluorescence. There were no such properties observed for 8-oxodeoxyguanosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 2’-deoxyguanosine, guanine, adenine, guanosine and 8-hydroxyadenine. These data imply that a free 8-oxoG base is more susceptible to oxidation than is its nucleoside form and, consequently, it stands as unique among intact and oxidatively modified purines. PMID:22198182

  7. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters sebaceous gland cell differentiation in vitro.

    PubMed

    Ju, Qiang; Fimmel, Sabine; Hinz, Norbert; Stahlmann, Ralf; Xia, Longqing; Zouboulis, Christos C

    2011-04-01

    Chloracne is a characteristic marker of intoxication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or related compounds. Decreased lipogenesis is a prominent clinical sign in this disease. However, the activity of dioxins on human sebaceous glands is still unclear. In this study, the effects of TCDD on sebaceous gland differentiation were studied both in human skin samples maintained ex vivo and in cultured SZ95 sebocytes. Aryl hydrocarbon receptor (AhR) protein expression, the receptor for dioxin, was detected in SZ95 sebocytes. Its expression was markedly inhibited by TCDD. Furthermore, we detected a reduced release of neutral lipids (10(-10) -10(-8) M; P<0.001) and decreased expression of epithelial membrane antigen and keratin 7, all of which are specific markers of sebaceous differentiation. Markedly, increased expression of the keratinocyte differentiation marker keratin 10 and of peroxisome proliferators-activated receptor-δ was assessed in SZ95 sebocytes treated with TCDD. To corroborate these in vitro data, an ex vivo sebaceous gland-rich skin culture model was investigated. Obvious shrinkage of sebaceous glands with sebaceous duct hyperplasia and increased expression of keratin 10 in the atrophic sebaceous glands were observed on the 5th day of TCDD treatment. In conclusion, TCDD affects the differentiation of sebaceous gland cells probably by switching human sebaceous into keratinocyte-like differentiation. In addition and together with the results of a parallel study (J Dermatol Sci 58, 2010, 211), we provide evidence that TCDD effects on human sebocytes are mediated through the AhR signalling pathway.

  8. State-space analysis of time-varying higher-order spike correlation for multiple neural spike train data.

    PubMed

    Shimazaki, Hideaki; Amari, Shun-Ichi; Brown, Emery N; Grün, Sonja

    2012-01-01

    Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e.g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods

  9. Effects of TrkB agonist 7,8-dihydroxyflavone on sensory gating deficits in mice after administration of methamphetamine.

    PubMed

    Ren, Qian; Zhang, Ji-Chun; Fujita, Yuko; Ma, Min; Wu, Jin; Hashimoto, Kenji

    2013-05-01

    Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway plays a role in behavioral abnormalities observed after administration of psychostimulants, such as methamphetamine (METH). This study was undertaken to examine whether the potent TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) could improve prepulse inhibition (PPI) deficits in mice seen after a single dose of METH. Treatment with 7,8-DHF (3.0, 10 or 30 mg/kg) improved PPI deficits in mice associated with exposure to METH (3.0 mg/kg), in a dose dependent manner. Furthermore, co-administration of ANA-12 (0.5 mg/kg), a TrkB antagonist, significantly blocked the effects of 7,8-DHF (30 mg/kg) on METH-induced PPI deficits. In contrast, administration of 5,7-dihydroxyflavone (5,7-DHF: 30 mg/kg), an inactive TrkB ligand, did not affect METH-induced PPI deficits in mice. An in vivo microdialysis study in conscious mice showed that 7,8-DHF (30 mg/kg) significantly attenuated increased dopamine release in the striatum, after METH administration (3 mg/kg). This study suggests that 7,8-DHF can improve PPI deficits in these mice, through the inhibition of METH-induced dopamine release. Therefore, it is likely that TrkB agonists, such as 7,8-DHF, may constitute a novel class of therapeutic drugs for neuropsychiatric diseases such as METH-use disorder and schizophrenia.

  10. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) plasma concentrations in residents of Paritutu, New Zealand: evidence of historical exposure.

    PubMed

    Fowles, J; Noonan, M; Stevenson, C; Baker, V; Gallagher, L; Read, D; Phillips, D

    2009-05-01

    An assessment of community exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was undertaken in Paritutu, New Zealand. The suburb lies adjacent to an agrichemical facility that produced 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), between 1962 and 1987. Soil TCDD measurements from 73 nearby addresses demonstrated a pattern of TCDD deposition consistent with an aerial plume following the prevailing local wind patterns and the agrichemical plant as the point source. Blood samples were taken from 52 volunteers having lived for three or more years in Paritutu between 1962 and 1987. Candidate selection focused primarily on individuals who were most likely to show elevated TCDD blood lipid levels when compared to age and gender stratified national average blood concentrations, and secondarily on individuals that provided additional information about specific exposure periods, potential exposures of younger age groups, and specific dietary patterns. A multipathway exposure model was used to estimate serum TCDD levels in each participant. Age and gender-specific TCDD elimination kinetics were also considered. Historical TCDD environmental concentrations were back-calculated from soil concentrations at each residence assuming TCDD releases occurred pre-dominantly between 1962 and 1975. Serum was analysed for chlorinated dibenzodioxins and dibenzofurans, and a subset was analysed for dioxin-like polychlorinated biphenyls. TCDD in serum lipid exceeded two standard deviations above national background levels for 14 participants, and 3 standard deviations for 10 participants. The highest TCDD lipid concentration was 33.3 ng/kg-lipid, or 11 times higher than the comparative 1997 national average. Elevated TCDD concentrations were observed primarily, but not exclusively, in the older study participants who had been in residence in Paritutu before 1968. The study demonstrated TCDD exposure in this community, occurring most likely through the aerial route, and most probably

  11. DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.

    PubMed

    Liu, Lin; De, Subhajyoti; Michor, Franziska

    2013-01-01

    Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes. Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features. Furthermore, some substitution signatures are more frequent in certain DNA replication timing zones. Finally, integrating data on higher-order nuclear organization, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves. These data suggest that DNA replication timing together with higher-order genomic organization contribute to the patterns of single-nucleotide substitution in normal and cancer genomes.

  12. Is the general conclusion justified that higher applicable field strength results in shorter analysis time with organic solvents in CE?

    PubMed

    Téllez, Adolfo; Kenndler, Ernst

    2009-11-01

    In this paper, a widespread opinion in CE with organic solvents for the background electrolyte is critically questioned, namely that in general a shorter analysis time can be achieved due to the higher field strength applicable compared with aqueous electrolyte systems. This view, common in the literature, is based on the supposition that the conductance in organic solvents is lower than in water. Indeed in many organic solvents with higher viscosity than water lower ion mobility is observed, and higher fields can be applied in these cases. However, in this paper the problem is sharper defined and treated two-fold: (i) in all solvents conditions are such that either the same electric power is generated, or (ii) the same temperature increase is taken into account. It was shown that for the same electric power the field strength in the organic solvent can be changed to a less extent than the ionic mobility changes. As a result, the migration velocity of the analytes is lower and the analysis time is longer in most organic solvents compared with water; acetonitrile (MeCN) is an exception (in this solvent the mobilities are higher than in water). The more stringent treatment of the problem takes an equal temperature increase due to Joule heating into account rather than equal electric power. The temperature increase in the capillary depends on the thermal conductivity of the solvent, which is only about one-third of that of water for organic liquids. The consequence is that in none of the organic solvent systems a shorter analysis time can be achieved compared with water (given that the experimental conditions are comparable, e.g. zero EOF). The theoretical predictions were confirmed by measurements with water, methanol, propylenecarbonate, and MeCN as solvents.

  13. Source modeling of the 2015 Mw 7.8 Nepal (Gorkha) earthquake sequence: Implications for geodynamics and earthquake hazards

    USGS Publications Warehouse

    McNamara, Daniel E.; Yeck, William; Barnhart, William D.; Schulte-Pelkum, V.; Bergman, E.; Adhikari, L. B.; Dixit, Amod; Hough, S.E.; Benz, Harley M.; Earle, Paul

    2016-01-01

    The Gorkha earthquake on April 25th, 2015 was a long anticipated, low-angle thrust-faulting event on the shallow décollement between the India and Eurasia plates. We present a detailed multiple-event hypocenter relocation analysis of the Mw 7.8 Gorkha Nepal earthquake sequence, constrained by local seismic stations, and a geodetic rupture model based on InSAR and GPS data. We integrate these observations to place the Gorkha earthquake sequence into a seismotectonic context and evaluate potential earthquake hazard.Major results from this study include (1) a comprehensive catalog of calibrated hypocenters for the Gorkha earthquake sequence; (2) the Gorkha earthquake ruptured a ~ 150 × 60 km patch of the Main Himalayan Thrust (MHT), the décollement defining the plate boundary at depth, over an area surrounding but predominantly north of the capital city of Kathmandu (3) the distribution of aftershock seismicity surrounds the mainshock maximum slip patch; (4) aftershocks occur at or below the mainshock rupture plane with depths generally increasing to the north beneath the higher Himalaya, possibly outlining a 10–15 km thick subduction channel between the overriding Eurasian and subducting Indian plates; (5) the largest Mw 7.3 aftershock and the highest concentration of aftershocks occurred to the southeast the mainshock rupture, on a segment of the MHT décollement that was positively stressed towards failure; (6) the near surface portion of the MHT south of Kathmandu shows no aftershocks or slip during the mainshock. Results from this study characterize the details of the Gorkha earthquake sequence and provide constraints on where earthquake hazard remains high, and thus where future, damaging earthquakes may occur in this densely populated region. Up-dip segments of the MHT should be considered to be high hazard for future damaging earthquakes.

  14. Source Mechanism of May 30, 2015 Bonin Islands, Japan Deep Earthquake (Mw7.8) Estimated by Broadband Waveform Modeling

    NASA Astrophysics Data System (ADS)

    Tsuboi, S.; Nakamura, T.; Miyoshi, T.

    2015-12-01

    May 30, 2015 Bonin Islands, Japan earthquake (Mw 7.8, depth 679.9km GCMT) was one of the deepest earthquakes ever recorded. We apply the waveform inversion technique (Kikuchi & Kanamori, 1991) to obtain slip distribution in the source fault of this earthquake in the same manner as our previous work (Nakamura et al., 2010). We use 60 broadband seismograms of IRIS GSN seismic stations with epicentral distance between 30 and 90 degrees. The broadband original data are integrated into ground displacement and band-pass filtered in the frequency band 0.002-1 Hz. We use the velocity structure model IASP91 to calculate the wavefield near source and stations. We assume that the fault is squared with the length 50 km. We obtain source rupture model for both nodal planes with high dip angle (74 degree) and low dip angle (26 degree) and compare the synthetic seismograms with the observations to determine which source rupture model would explain the observations better. We calculate broadband synthetic seismograms with these source propagation models using the spectral-element method (Komatitsch & Tromp, 2001). We use new Earth Simulator system in JAMSTEC to compute synthetic seismograms using the spectral-element method. The simulations are performed on 7,776 processors, which require 1,944 nodes of the Earth Simulator. On this number of nodes, a simulation of 50 minutes of wave propagation accurate at periods of 3.8 seconds and longer requires about 5 hours of CPU time. Comparisons of the synthetic waveforms with the observation at teleseismic stations show that the arrival time of pP wave calculated for depth 679km matches well with the observation, which demonstrates that the earthquake really happened below the 660 km discontinuity. In our present forward simulations, the source rupture model with the low-angle fault dipping is likely to better explain the observations.

  15. Dynamics of a Solar Prominence Tornado Observed by SDO/AIA on 2012 November 7-8

    NASA Astrophysics Data System (ADS)

    Mghebrishvili, Irakli; Zaqarashvili, Teimuraz V.; Kukhianidze, Vasil; Ramishvili, Giorgi; Shergelashvili, Bidzina; Veronig, Astrid; Poedts, Stefaan

    2015-09-01

    We study the detailed dynamics of a solar prominence tornado using time series of 171, 304, 193, and 211 Å spectral lines obtained by the Solar Dynamics Observatory/Atmospheric Imaging Assembly during 2012 November 7-8. The tornado first appeared at 08:00 UT, November 07, near the surface, gradually rose upwards with the mean speed of ˜1.5 km s-1 and persisted over 30 hr. Time-distance plots show two patterns of quasi-periodic transverse displacements of the tornado axis with periods of 40 and 50 minutes at different phases of the tornado evolution. The first pattern occurred during the rising phase and can be explained by the upward motion of the twisted tornado. The second pattern occurred during the later stage of evolution when the tornado already stopped rising and could be caused either by MHD kink waves in the tornado or by the rotation of two tornado threads around a common axis. The later hypothesis is supported by the fact that the tornado sometimes showed a double structure during the quasi-periodic phase. 211 and 193 Å spectral lines show a coronal cavity above the prominence/tornado, which started expansion at ˜13:00 UT and continuously rose above the solar limb. The tornado finally became unstable and erupted together with the corresponding prominence as coronal mass ejection (CME) at 15:00 UT, November 08. The final stage of the evolution of the cavity and the tornado-related prominence resembles the magnetic breakout model. On the other hand, the kink instability may destabilize the twisted tornado, and consequently prominence tornadoes can be used as precursors for CMEs.

  16. The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens

    NASA Technical Reports Server (NTRS)

    Ferrario, J.; Byrne, C.

    2000-01-01

    The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.

  17. A High-Order, Linear Time-Invariant Model for Application to Higher Harmonic Control and Flight Control System Interaction

    NASA Technical Reports Server (NTRS)

    Cheng, Rendy P.; Tischler, Mark B.; Celi, Roberto

    2006-01-01

    This research describes a new methodology for the extraction of a high-order, linear time invariant model, which allows the periodicity of the helicopter response to be accurately captured. This model provides the needed level of dynamic fidelity to permit an analysis and optimization of the AFCS and HHC algorithms. The key results of this study indicate that the closed-loop HHC system has little influence on the AFCS or on the vehicle handling qualities, which indicates that the AFCS does not need modification to work with the HHC system. However, the results show that the vibration response to maneuvers must be considered during the HHC design process, and this leads to much higher required HHC loop crossover frequencies. This research also demonstrates that the transient vibration responses during maneuvers can be reduced by optimizing the closed-loop higher harmonic control algorithm using conventional control system analyses.

  18. Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1.

    PubMed

    Li, Yan; Mei, Hu; Wu, Qiangen; Zhang, Suhui; Fang, Jia-Long; Shi, Leming; Guo, Lei

    2011-12-01

    Kava is a plant traditionally used for making beverages in Pacific Basin countries and has been used for the treatment of nervous disorders in the United States. The pharmacological activity of kava is achieved through kavalactones in kava extract, which include kawain, 7,8-dihydrokawain, yangonin, 5,6-dehydrokawain, methysticin, and 7,8-dihydromethysticin. Recent studies have shown that kava extract induces hepatic CYP1A1 enzyme; however, the mechanisms of CYP1A1 induction have not been elucidated, and the kavalactones responsible for CYP1A1 induction have not yet been identified. Using a combination of biochemical assays and molecular docking tools, we determined the functions of kava extract and kavalactones and delineated the underlying mechanisms involved in CYP1A1 induction. The results showed that kava extract displayed a concentration-dependent effect on CYP1A1 induction. Among the six major kavalactones, methysticin triggered the most profound inducing effect on CYP1A1 followed by 7,8-dihydromethysticin. The other four kavalactones (yangonin, 5,6-dehydrokawain, kawain, and 7,8-dihydrokawain) did not show significant effects on CYP1A1. Consistent with the experimental results, in silico molecular docking studies based on the aryl hydrocarbon receptor (AhR)-ligand binding domain homology model also revealed favorable binding to AhR for methysticin and 7,8-dihydromethysticin compared with the remaining kavalactones. Additionally, results from a luciferase gene reporter assay suggested that kava extract, methysticin, and 7,8-dihydromethysticin were able to activate the AhR signaling pathway. Moreover, kava extract-, methysticin-, and 7,8-dihydromethysticin-mediated CYP1A1 induction was blocked by an AhR antagonist and abolished in AhR-deficient cells. These findings suggest that kava extract induces the expression of CYP1A1 via an AhR-dependent mechanism and that methysticin and 7,8-dihydromethysticin contribute to CYP1A1 induction. The induction of CYP1A1

  19. Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages

    PubMed Central

    Suzuki, Shiho; Mimuro, Hitomi; Kim, Minsoo; Ogawa, Michinaga; Ashida, Hiroshi; Toyotome, Takahito; Franchi, Luigi; Suzuki, Masato; Sanada, Takahito; Suzuki, Toshihiko; Tsutsui, Hiroko; Núñez, Gabriel; Sasakawa, Chihiro

    2014-01-01

    When nucleotide-binding oligomerization domain–like receptors (NLRs) sense cytosolic-invading bacteria, they induce the formation of inflammasomes and initiate an innate immune response. In quiescent cells, inflammasome activity is tightly regulated to prevent excess inflammation and cell death. Many bacterial pathogens provoke inflammasome activity and induce inflammatory responses, including cell death, by delivering type III secreted effectors, the rod component flagellin, and toxins. Recent studies indicated that Shigella deploy multiple mechanisms to stimulate NLR inflammasomes through type III secretion during infection. Here, we show that Shigella induces rapid macrophage cell death by delivering the invasion plasmid antigen H7.8 (IpaH7.8) enzyme 3 (E3) ubiquitin ligase effector via the type III secretion system, thereby activating the NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasomes and caspase-1 and leading to macrophage cell death in an IpaH7.8 E3 ligase-dependent manner. Mice infected with Shigella possessing IpaH7.8, but not with Shigella possessing an IpaH7.8 E3 ligase-null mutant, exhibited enhanced bacterial multiplication. We defined glomulin/flagellar-associated protein 68 (GLMN) as an IpaH7.8 target involved in IpaH7.8 E3 ligase-dependent inflammasome activation. This protein originally was identified through its association with glomuvenous malformations and more recently was described as a member of a Cullin ring ligase inhibitor. Modifying GLMN levels through overexpression or knockdown led to reduced or augmented inflammasome activation, respectively. Macrophages stimulated with lipopolysaccharide/ATP induced GLMN puncta that localized with the active form of caspase-1. Macrophages from GLMN+/− mice were more responsive to inflammasome activation than those from GLMN+/+ mice. Together, these results highlight a unique bacterial adaptation that hijacks inflammasome activation via

  20. Less Time to Study, Less Well Prepared for Work, yet Satisfied with Higher Education: A UK Perspective on Links between Higher Education and the Labour Market

    ERIC Educational Resources Information Center

    Little, Brenda; Arthur, Lore

    2010-01-01

    This paper explores graduates' views on the relationship between higher education and employment. It draws on a major European study involving graduates five years after graduation and highlights similarities and differences between UK graduates' experiences and their European counterparts. Specifically, we address questions raised in the study…

  1. State-Space Analysis of Time-Varying Higher-Order Spike Correlation for Multiple Neural Spike Train Data

    PubMed Central

    Shimazaki, Hideaki; Amari, Shun-ichi; Brown, Emery N.; Grün, Sonja

    2012-01-01

    Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e.g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods

  2. Neutron structure of human carbonic anhydrase II: A hydrogen bonded water network switch is observed between pH 7.8 and 10.0.

    SciTech Connect

    Fisher, Zoe; Langan, Paul; Mustyakimov, Marat; Kovalevsky, Andrey

    2011-01-01

    The neutron structure of wild type human carbonic anhydrase II at pH 7.8 has been determined to 2.0 resolution. Detailed analysis and comparison to the previous determined structure at pH 10.0 shows important differences in protonation of key catalytic residues in the active site as well as a rearrangement of the hydrogen bonded water network. For the first time, a completed hydrogen bonded network stretching from the Zn-bound solvent to the proton shuttling residue His64 has been directed observed.

  3. Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network "switch" is observed between pH 7.8 and 10.0.

    PubMed

    Fisher, Zoë; Kovalevsky, Andrey Y; Mustyakimov, Marat; Silverman, David N; McKenna, Robert; Langan, Paul

    2011-11-08

    The neutron structure of wild-type human carbonic anhydrase II at pH 7.8 has been determined to 2.0 Å resolution. Detailed analysis and comparison to the previously determined structure at pH 10.0 show important differences in the protonation of key catalytic residues in the active site as well as a rearrangement of the H-bonded water network. For the first time, a completed H-bonded network stretching from the Zn-bound solvent to the proton shuttling residue, His64, has been directly observed.

  4. Inter-strain heterogeneity in rat hepatic transcriptomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    SciTech Connect

    Yao, Cindy Q.; Prokopec, Stephenie D.; Watson, John D.; Pang, Renee; P'ng, Christine; Chong, Lauren C.; Harding, Nicholas J.; Pohjanvirta, Raimo; Okey, Allan B.; Boutros, Paul C.

    2012-04-15

    The biochemical and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been the subject of intense study for decades. It is now clear that essentially all TCDD-induced toxicities are mediated by DNA–protein interactions involving the Aryl Hydrocarbon Receptor (AHR). Nevertheless, it remains unknown which AHR target genes cause TCDD toxicities. Several groups, including our own, have developed rodent model systems to probe these questions. mRNA expression profiling of these model systems has revealed significant inter-species heterogeneity in rodent hepatic responses to TCDD. It has remained unclear if this variability also exists within a species, amongst rodent strains. To resolve this question, we profiled the hepatic transcriptomic response to TCDD of diverse rat strains (L-E, H/W, F344 and Wistar rats) and two lines derived from L-E × H/W crosses, at consistent age, sex, and dosing (100 μg/kg TCDD for 19 h). Using this uniquely consistent dataset, we show that the majority of TCDD-induced alterations in mRNA abundance are strain/line-specific: only 11 genes were affected by TCDD across all strains, including well-known dioxin-responsive genes such as Cyp1a1 and Nqo1. Our analysis identified two novel universally dioxin-responsive genes as well as 4 genes induced by TCDD in dioxin-sensitive rats only. These 6 genes are strong candidates to explain TCDD-related toxicities, so we validated them using 152 animals in time-course (0 to 384 h) and dose–response (0 to 3000 μg/kg) experiments. This study reveals that different rat strains exhibit dramatic transcriptional heterogeneity in their hepatic responses to TCDD and that inter-strain comparisons can help identify candidate toxicity-related genes.

  5. Combination reactions of superoxide with 8-Oxo-7,8-dihydroguanine radicals in DNA: kinetics and end products.

    PubMed

    Misiaszek, Richard; Uvaydov, Yuriy; Crean, Conor; Geacintov, Nicholas E; Shafirovich, Vladimir

    2005-02-25

    One of the major biomarkers of oxidative stress and oxidative damage of cellular DNA is 8-oxo-7,8-dihydroguanine (8-oxoGua), which is more easily oxidized than guanine to diverse oxidative products. In this work, we have investigated further oxidative transformations of 8-oxoGua in single- and double-stranded oligonucleotides to the dehydroguanidinohydantoin, oxaluric acid, and diastereomeric spiroiminodihydantoin lesions. The relative distributions of these end products were explored by a combined kinetic laser spectroscopy and mass spectrometry approach and are shown to depend markedly on the presence of superoxide radical anions. The 8-oxaGua radicals were produced by one-electron oxidation of 8-oxoGua by 2-aminopurine radicals generated by the two-photon ionization of 2-aminopurine residues site specifically positioned in 5'-d(CC[2-aminopurine]TC[8-oxoGua]CTACC). The hydrated electrons also formed in the photoionization process were trapped by dissolved molecular oxygen thus producing superoxide. A combination reaction between the 8-oxoGua and superoxide radicals occurs with the rate constant of (1.3 +/- 0.2) x 10(8) m(-1) s(-1) and (1.0 +/- 0.5) x 10(8) m(-1) s(-1) in single- and double-stranded DNA, respectively. The major end products of this reaction are the dehydroguanidinohydantoin lesions that slowly hydrolyze to oxaluric acid residues. In the presence of Cu,Zn-superoxide dismutase, an enzyme that induces the rapid catalytic dismutation of superoxide to the less reactive H(2)O(2) and O(2), the yields of the dehydroguanidinohydantion lesions become negligible. Under these conditions, the 8-oxoGua radicals do not exhibit any observable reactivities with oxygen (k < 10(2) m(-1) s(-1)), decay on the time interval of several seconds, and the major reaction products are the spiroiminodihydantoin lesions. The possible biological implications of the 8-oxoGua oxidation are discussed.

  6. 2,3,7,8-Tetrachlorodibenzo-p-dioxin Upregulates FoxQ1b in Zebrafish Jaw Primordium

    PubMed Central

    Planchart, Antonio; Mattingly, Carolyn J.

    2010-01-01

    Vertebrate jaw development can be disrupted by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—a potent activator of the aryl hydrocarbon receptor (AHR) transcription factor required for transducing the toxic effects of TCDD. We used zebrafish (Danio rerio) embryos to investigate transcriptional responses to TCDD with the goal of discovering novel, jaw-specific genes affected by TCDD exposure. Our results uncovered a novel target of TCDD-activated Ahr belonging to the evolutionarily conserved family of forkhead box transcription factors. Quantitative real-time polymerase chain reaction analysis demonstrated that FoxQ1b was upregulated by TCDD 7- and 10-fold at 24 and 48 h postfertilization (hpf), respectively. The rate of TCDD-induced FoxQ1b expression was more rapid than that of Cyp1a, a known direct target of TCDD-activated Ahr. TCDD-mediated induction of FoxQ1b was suppressed in the presence of an Ahr antagonist, α-naphthoflavone, as well as following knockdown of Ahr2 expression using an Ahr2-specific morpholino antisense oligonucleotide. In situ hybridization analysis of FoxQ1b expression at 48 hpf demonstrated that FoxQ1b is specifically expressed in the jaw primordium where it discretely outlines a developing jaw structure known as Meckel’s cartilage—a conserved structure in all jawed vertebrates that develops abnormally in the presence of TCDD. These results identify a novel target of TCDD-activated Ahr and suggest that FoxQ1b may play a role in craniofacial abnormalities induced by developmental exposure to TCDD. PMID:20055451

  7. A comparison of observed and predicted ground motions from the 2015 MW7.8 Gorkha, Nepal, earthquake

    USGS Publications Warehouse

    Hough, Susan E.; Martin, Stacey S.; Gahalaut, V.; Joshi, A.; Landes, M.; Bossu, R.

    2016-01-01

    We use 21 strong motion recordings from Nepal and India for the 25 April 2015 moment magnitude (MW) 7.8 Gorkha, Nepal, earthquake together with the extensive macroseismic intensity data set presented by Martin et al. (Seism Res Lett 87:957–962, 2015) to analyse the distribution of ground motions at near-field and regional distances. We show that the data are consistent with the instrumental peak ground acceleration (PGA) versus macroseismic intensity relationship developed by Worden et al. (Bull Seism Soc Am 102:204–221, 2012), and use this relationship to estimate peak ground acceleration from intensities (PGAEMS). For nearest-fault distances (RRUP < 200 km), PGAEMS is consistent with the Atkinson and Boore (Bull Seism Soc Am 93:1703–1729, 2003) subduction zone ground motion prediction equation (GMPE). At greater distances (RRUP > 200 km), instrumental PGA values are consistent with this GMPE, while PGAEMS is systematically higher. We suggest the latter reflects a duration effect whereby effects of weak shaking are enhanced by long-duration and/or long-period ground motions from a large event at regional distances. We use PGAEMS values within 200 km to investigate the variability of high-frequency ground motions using the Atkinson and Boore (Bull Seism Soc Am 93:1703–1729, 2003) GMPE as a baseline. Across the near-field region, PGAEMS is higher by a factor of 2.0–2.5 towards the northern, down-dip edge of the rupture compared to the near-field region nearer to the southern, up-dip edge of the rupture. Inferred deamplification in the deepest part of the Kathmandu valley supports the conclusion that former lake-bed sediments experienced a pervasive nonlinear response during the mainshock (Dixit et al. in Seismol Res Lett 86(6):1533–1539, 2015; Rajaure et al. in Tectonophysics, 2016. Ground motions were significantly amplified in the southern Gangetic basin, but were relatively low in the northern basin. The overall distribution of ground motions

  8. Higher level phylogeny and the first divergence time estimation of Heteroptera (Insecta: Hemiptera) based on multiple genes.

    PubMed

    Li, Min; Tian, Ying; Zhao, Ying; Bu, Wenjun

    2012-01-01

    Heteroptera, or true bugs, are the largest, morphologically diverse and economically important group of insects with incomplete metamorphosis. However, the phylogenetic relationships within Heteroptera are still in dispute and most of the previous studies were based on morphological characters or with single gene (partial or whole 18S rDNA). Besides, so far, divergence time estimates for Heteroptera totally rely on the fossil record, while no studies have been performed on molecular divergence rates. Here, for the first time, we used maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) with multiple genes (18S rDNA, 28S rDNA, 16S rDNA and COI) to estimate phylogenetic relationships among the infraorders, and meanwhile, the Penalized Likelihood (r8s) and Bayesian (BEAST) molecular dating methods were employed to estimate divergence time of higher taxa of this suborder. Major results of the present study included: Nepomorpha was placed as the most basal clade in all six trees (MP trees, ML trees and Bayesian trees of nuclear gene data and four-gene combined data, respectively) with full support values. The sister-group relationship of Cimicomorpha and Pentatomomorpha was also strongly supported. Nepomorpha originated in early Triassic and the other six infraorders originated in a very short period of time in middle Triassic. Cimicomorpha and Pentatomomorpha underwent a radiation at family level in Cretaceous, paralleling the proliferation of the flowering plants. Our results indicated that the higher-group radiations within hemimetabolous Heteroptera were simultaneously with those of holometabolous Coleoptera and Diptera which took place in the Triassic. While the aquatic habitat was colonized by Nepomorpha already in the Triassic, the Gerromorpha independently adapted to the semi-aquatic habitat in the Early Jurassic.

  9. Role of higher excited electronic states on high harmonic generation in H2(+)--a time-independent Hermitian Floquet approach.

    PubMed

    Sarkar, Chitrakshya; Bhattacharyya, S S; Saha, Samir

    2011-01-14

    We have theoretically studied the role of high-lying molecular electronic states on the high harmonic generation (HHG) in H(2)(+) within the framework of a time-independent Hermitian nonperturbative three-dimensional Floquet technique for continuous wave monochromatic lasers of intensities of 2.59 × 10(13), 4.0 × 10(13), and 5.6 × 10(13) W∕cm(2), and wavelengths of 1064, 532, and 355 nm. To evaluate the HHG spectra, the resonance Floquet quasienergy and the Fourier components of the Floquet state corresponding to the initial vibrational-rotational level v = 0, J = 0 have been computed by solving the time-independent close-coupled Schrödinger equation following the Floquet method. The calculations include seven molecular electronic states in the basis set expansion of the Floquet state. The electronic states considered, apart from the two lowest 1sσ(g) and 2pσ(u) states, are 2pπ(u), 2sσ(g), 3pσ(u), 3dσ(g), and 4fσ(u). All the concerned higher excited molecular electronic states asymptotically degenerate into the atomic state H(2 l) with l = 0, 1. The computations reveal signature of significant oscillations in the HHG spectra due to the interference effect of the higher molecular electronic states for all the considered laser intensities and wavelengths. We have attempted to explain, without invoking any ionization, the dynamics of HHG in H(2)(+) within the framework of electronic transitions due to the electric dipole moments and the nuclear motions on the field coupled ground, the first and the higher excited electronic states of this one-electron molecular ion.

  10. TERATOGENIC RESPONSES OF TGFALPHA KNOCKOUT FETUSES TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    EPA Science Inventory

    ABBOTT1, B.D., A.R. BUCKALEW1, and P.L. BRYANT2. 1Reproductive Toxicology Division, EPA, RAP, NC; 2Dept. Environ. Sciences & Engineering, UNC, Chapel Hill, NC. Teratogenic responses of TGF knockout fetuses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    TCDD induces cl...

  11. FORMATION OF 8-OXO-7, 8-DIHYDRO-2'-DEOXYGUANOSINE IN RAT LUNG FOLLOWING SUB-CHRONIC INHALATION OF CARBON BLACK

    EPA Science Inventory

    ABSTRACT
    Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative adduct in the lung DNA of rats following sub-chronic inhalation of carbon black. Gallagher, J., Sams II, R.L., Inmon, J., Gelein, R., Elder, A., Oberdorster, G., Prahalad, A. (2002). Toxicol. Appl. Pharm...

  12. CYP1A2 IS NOT REQUIRED FOR 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED IMMUNOSUPPRESSION

    EPA Science Inventory

    ABSTRACT
    One of the most sensitive and reproducible immunotoxic endpoints of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) exposure is suppression of the antibody response to sheep red blood cells (SRBCs) in mice. Immunosuppression occurs in concert with hepatomegaly and associ...

  13. THE CONCENTRATION AND DISTRIBUTION OF 2,3,7,8-DIBENZO-P-DIOXINS / - FURANS IN CHICKENS

    EPA Science Inventory

    The concentrations of 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid-adju...

  14. Percutaneous Absorption of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) From Soil (Journal Article)

    EPA Science Inventory

    Eight dermal absorption (two in vivo; six in vitro) and one intravenous experiment were conducted using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either neat (high dose at ~250 µg/cm2 and low dose at 10 ng/cm2) or sorbed on a low organic (LOS) or high organic (HOS) soil at 1 ppm...

  15. Detoxication of benzo[a]pyrene-7,8-dione by sulfotransferases (SULTs) in human lung cells.

    PubMed

    Zhang, Li; Huang, Meng; Blair, Ian A; Penning, Trevor M

    2012-08-24

    Polycyclic aromatic hydrocarbons (PAH) are environmental and tobacco carcinogens. Human aldo-keto reductases catalyze the metabolic activation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active o-quinones. Benzo[a]pyrene-7,8-dione a representative PAH o-quinone is reduced back to the corresponding catechol to generate a futile redox-cycle. We investigated whether sulfonation of PAH catechols by human sulfotransferases (SULT) could intercept the catechol in human lung cells. RT-PCR identified SULT1A1, -1A3, and -1E1 as the isozymes expressed in four human lung cell lines. The corresponding recombinant SULTs were examined for their substrate specificity. Benzo[a]pyrene-7,8-dione was reduced to benzo[a]pyrene-7,8-catechol by dithiothreitol under anaerobic conditions and then further sulfonated by the SULTs in the presence of 3'-[(35)S]phosphoadenosine 5'-phosphosulfate as the sulfonate group donor. The human SULTs catalyzed the sulfonation of benzo[a]pyrene-7,8-catechol and generated two isomeric benzo[a]pyrene-7,8-catechol O-monosulfate products that were identified by reversed phase HPLC and by LC-MS/MS. The various SULT isoforms produced the two isomers in different proportions. Two-dimensional (1)H and (13)C NMR assigned the two regioisomers of benzo[a]pyrene-7,8-catechol monosulfate as 8-hydroxy-benzo[a]pyrene-7-O-sulfate (M1) and 7-hydroxy-benzo[a]pyrene-8-O-sulfate (M2), respectively. The kinetic profiles of three SULTs were different. SULT1A1 gave the highest catalytic efficiency (k(cat)/K(m)) and yielded a single isomeric product corresponding to M1. By contrast, SULT1E1 showed distinct substrate inhibition and formed both M1 and M2. Based on expression levels, catalytic efficiency, and the fact that the lung cells only produce M1, it is concluded that the major isoform that can intercept benzo[a]pyrene-7,8-catechol is SULT1A1.

  16. Blind deconvolution of the seismic source time function based on higher order statistics of regional coda waves

    NASA Astrophysics Data System (ADS)

    Sèbe, Olivier; Guilbert, Jocelyn; Bard, Pierre-Yves

    2010-05-01

    Recovering the source time function (STF) of a seismic event provides essential information on the nature and physical mechanisms of the source. Nevertheless, the broad-band estimation of STF is often a difficult task particularly at regional distance where the unknown high heterogeneity of the crustal limits wave inversion to the low frequency content of the source. On the other hand, the widely used empirical Green's function (EGF) suffers from certain limitations towards the selection of valuable empirical green function, especially for small events. Several studies have proved the usefulness of the S coda wave for source parameter estimation such as its moment or its power spectrum. Unfortunately, as these methods are based on second order statistics (power spectrum), the phase of the source spectrum is lost as well as the event STF. In this study, we have developed an original method to recover STF based on the higher order statistic (HOS) blind deconvolution of the S wave coda excitation. Under the assumption that the coda excitation time series is a non-Gaussian independent and identically distributed random signal, this higher order spectral approach provides the amplitude and especially the phase of source spectrum, allowing thus the complete estimation of the seismic STF. We propose a two step algorithm to recover the seismic STF: first, the diffuse coda wave field is whitened to remove the non-stationary attenuation effect; second the STF of the event is estimated from the HOS of the whitened coda excitation such as its bicorrelation and tricorrelation. This algorithm has been tested on regional records of the Rambervillers, 22/02/2003, Ml=5.4 earthquake, located in North-east of France. As the convergence rate of the higher order statistic is slower than second order one, their estimation requires rather long time series and high signal to noise ratio. In order to improve the signal to noise ratio for HOS estimation, a multi-stations stacking procedure

  17. Invitational Conference on College Prepayment and Savings Plans (Denver, Colorado, June 7-8, 1987). Summary.

    ERIC Educational Resources Information Center

    College Entrance Examination Board, New York, NY.

    Summaries of conference presentations on college savings and prepayment plans and related tax, policy, and social issues are provided. The conference objective was to communicate the issues to constituents with the most at stake: parents, students, and relatives; state and federal legislators and staff; and developers of plans for higher education…

  18. Changes in mouse mu opioid receptor exon 7/8-like immunoractivity following food restriction and food deprivation in rats

    PubMed Central

    Hadjimarkou, Maria M.; Abbadie, Catherine; Kasselman, Lora; Pan, Ying-Xian; Pasternak, Gavril W.; Bodnar, Richard J.

    2009-01-01

    Opioid agonists and antagonists respectively increase and decrease food intake. That selective mu opioid antagonists are more effective than antisense probes directed against the mu opioid receptor (MOR-1) gene in reducing deprivation-induced feeding suggests a role for isoforms. Both food restriction and deprivation alter protein and mRNA levels of opioid peptides and receptors. Antisera directed against exon 4 of the MOR-1-like immunoreactivity (LI) (Exon 4) clone or directed against mouse exons 7/8 (mE7/8-LI) revealed high levels of immunoreactivity in brain nuclei related to feeding behavior. Therefore, the present study assessed MOR-1LI and mE7/8-LI in hypothalamic and extra-hypothalamic sites in rats exposed to ad libitum feeding, food restriction (2, 7, 14 days) or food deprivation (24, 48 h). MOR-1-LI displayed robust reactivity, but was insensitive to food restriction or deprivation. mE7/8-LI, both in terms of cell counts and relative optical density, was significantly and selectively increased in the dorsal and ventral parvocellular subdivisions of the hypothalamic paraventricular nucleus in food-restricted (14 days) rats, but all other restriction or deprivation regimens were ineffective in other hypothalamic nuclei. In contrast, significant and site-specific decreases in relative optical density in the rostral part of the nucleus tractus solitarius were observed in food-restricted (2, 7 days) or food-deprived (24, 48 h) animals, but these regimens were ineffective in the other extrahypothalamic sites. This study indicates the sensitivity of this mE7/8-LI probe in the hypothalamic parvocellular paraventricular nucleus and rostral nucleus tractus solitarius to food restriction and deprivation in rats. PMID:19301417

  19. Genotoxicity of styrene-7,8-oxide and styrene in Fisher 344 rats: a 4-week inhalation study.

    PubMed

    Gaté, Laurent; Micillino, Jean-Claude; Sébillaud, Sylvie; Langlais, Cristina; Cosnier, Frédéric; Nunge, Hervé; Darne, Christian; Guichard, Yves; Binet, Stéphane

    2012-06-20

    The cytogenetic alterations in leukocytes and the increased risk for leukemia, lymphoma, or all lymphohematopoietic cancer observed in workers occupationally exposed to styrene have been associated with its hepatic metabolisation into styrene-7,8-oxide, an epoxide which can induce DNA damages. However, it has been observed that styrene-7,8-oxide was also found in the atmosphere of reinforced plastic industries where large amounts of styrene are used. Since the main route of exposure to these compounds is inhalation, in order to gain new insights regarding their systemic genotoxicity, Fisher 344 male rats were exposed in full-body inhalation chambers, 6 h/day, 5 days/week for 4 weeks to styrene-7,8-oxide (25, 50, and 75 ppm) or styrene (75, 300, and 1000 ppm). Then, the induction of micronuclei in circulating reticulocytes and DNA strand breaks in leukocytes using the comet assay was studied at the end of the 3rd and 20th days of exposure. Our results showed that neither styrene nor styrene-7,8-oxide induced a significant increase of the micronucleus frequency in reticulocytes or DNA strand breaks in white blood cells. However, in the presence of the formamidopyridine DNA glycosylase, an enzyme able to recognize and excise DNA at the level of some oxidized DNA bases, a significant increase of DNA damages was observed at the end of the 3rd day of treatment in leukocytes from rats exposed to styrene but not to styrene-7,8-oxide. This experimental design helped to gather new information regarding the systemic genotoxicity of these two chemicals and may be valuable for the risk assessment associated with an occupational exposure to these molecules.

  20. Introducing conjoint analysis method into delayed lotteries studies: its validity and time stability are higher than in adjusting

    PubMed Central

    Białek, Michał; Markiewicz, Łukasz; Sawicki, Przemysław

    2015-01-01

    The delayed lotteries are much more common in everyday life than are pure lotteries. Usually, we need to wait to find out the outcome of the risky decision (e.g., investing in a stock market, engaging in a relationship). However, most research has studied the time discounting and probability discounting in isolation using the methodologies designed specifically to track changes in one parameter. Most commonly used method is adjusting, but its reported validity and time stability in research on discounting are suboptimal. The goal of this study was to introduce the novel method for analyzing delayed lotteries—conjoint analysis—which hypothetically is more suitable for analyzing individual preferences in this area. A set of two studies compared the conjoint analysis with adjusting. The results suggest that individual parameters of discounting strength estimated with conjoint have higher predictive value (Study 1 and 2), and they are more stable over time (Study 2) compared to adjusting. We discuss these findings, despite the exploratory character of reported studies, by suggesting that future research on delayed lotteries should be cross-validated using both methods. PMID:25674069

  1. Floods of August 7-8, 1979, in Chautauqua County, New York, with hydraulic analysis of Canadaway Creek in the village of Fredonia

    USGS Publications Warehouse

    Lumia, Richard; Johnston, W.H.

    1984-01-01

    Extensive flooding of streams in Chautauqua County, N.Y., on August 7-8, 1979, after severe thunderstorms, resulted in one death and millions of dollars worth of property damage. Severe flooding was reported on Canadaway Creek in Fredonia, where the peak discharge was computed to be 12,000 cubic feet per second. The recurrence interval of this discharge is estimated to be greater than 100 years (exceedance probability less than 0.01). A hydraulic analysis of the flood in Fredonia indicated that a debris jam at the Water Street bridge caused the water level (as determined from floodmarks) immediately upstream from the bridge to be 2.9 feet higher than level computed for unobstructed (without debris) flow conditions. The 100-year flood discharge at the Water Street bridge is computed to be 5,280 cubic feet per second, and the corresponding water level just upstream from the bridge (under unobstructed flow conditions) is 5.9 feet lower than the level observed during the August 7-8, 1979 flood. (USGS)

  2. Estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using a minimal physiologic toxicokinetic model.

    PubMed Central

    Thomaseth, K; Salvan, A

    1998-01-01

    In this study we investigated estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on a minimal physiologic toxicokinetic model in humans. Our purpose was to obtain a mathematical tool for dose-response studies based on human data. We first simplified an existing model of TCDD kinetics in humans and estimated its parameters (i.e., liver elimination and background input of TCDD) using repeated measures of serum dioxin taken in Vietnam veterans (Ranch Hand data and data from an unexposed reference group). We carried out computer simulation and estimation of the model parameters both under a nonlinear weighted least-squares model (naive pooled data approach) and under a nonlinear mixed-effects model. The best parameter estimates were obtained with log-transformed data under a mixed-effects model: liver elimination parameter kf = 0.022 days-1 (95% confidence interval [CI] = 0.020, 0.024), and background input rate input = 0.1251 pg/kg/day (95% CI = 0.071, 0.179). The dioxin kinetic model and its estimated parameters were then used to provide dose estimates for a cohort of workers with exposure to TCDD at chemical plants in the United States. First, the model was used to estimate the rate of occupational intake of TCDD in a subset of the cohort consisting of 253 subjects for whom one measure of serum TCDD was available. A model of change in body-mass index over time was also identified for this subsample. The occupational exposure rate was estimated by linear regression using the above values of kinetic parameters and assuming an initial condition for serum TCDD of 7 ppt, i.e., the average level found in unexposed workers. The estimate of the occupational exposure parameter was 232.7 pg/kg/day (95% CI 192, 273). This value can be applied to the full cohort to obtain for each cohort member the time course of serum dioxin concentration from which exposure indices can be derived. Sensitivity coefficients to model parameters (background

  3. Computer-mediated communication and time pressure induce higher cardiovascular responses in the preparatory and execution phases of cooperative tasks.

    PubMed

    Costa Ferrer, Raquel; Serrano Rosa, Miguel Ángel; Zornoza Abad, Ana; Salvador Fernández-Montejo, Alicia

    2010-11-01

    The cardiovascular (CV) response to social challenge and stress is associated with the etiology of cardiovascular diseases. New ways of communication, time pressure and different types of information are common in our society. In this study, the cardiovascular response to two different tasks (open vs. closed information) was examined employing different communication channels (computer-mediated vs. face-to-face) and with different pace control (self vs. external). Our results indicate that there was a higher CV response in the computer-mediated condition, on the closed information task and in the externally paced condition. These role of these factors should be considered when studying the consequences of social stress and their underlying mechanisms.

  4. Information transfer across the scales of climate variability: The effect of the 7-8 year cycle on the annual and interannual scales

    NASA Astrophysics Data System (ADS)

    Palus, Milan; Jajcay, Nikola; Hlinka, Jaroslav; Kravtsov, Sergey; Tsonis, Anastasios

    2016-04-01

    Complexity of the climate system stems not only from the fact that it is variable over a huge range of spatial and temporal scales, but also from the nonlinear character of the climate system that leads to interactions of dynamics across scales. The dynamical processes on large time scales influence variability on shorter time scales. This nonlinear phenomenon of cross-scale causal interactions can be observed due to the recently introduced methodology [1] which starts with a wavelet decomposition of a multi-scale signal into quasi-oscillatory modes of a limited bandwidth, described using their instantaneous phases and amplitudes. Then their statistical associations are tested in order to search for interactions across time scales. An information-theoretic formulation of the generalized, nonlinear Granger causality [2] uncovers causal influence and information transfer from large-scale modes of climate variability with characteristic time scales from years to almost a decade to regional temperature variability on short time scales. In analyses of air temperature records from various European locations, a quasioscillatory phenomenon with the period around 7-8 years has been identified as the factor influencing variability of surface air temperature (SAT) on shorter time scales. Its influence on the amplitude of the SAT annual cycle was estimated in the range 0.7-1.4 °C and the effect on the overall variability of the SAT anomalies (SATA) leads to the changes 1.5-1.7 °C in the annual SATA means. The strongest effect of the 7-8 year cycle was observed in the winter SATA means where it reaches 4-5 °C in central European station and reanalysis data [3]. This study is supported by the Ministry of Education, Youth and Sports of the Czech Republic within the Program KONTAKT II, Project No. LH14001. [1] M. Palus, Phys. Rev. Lett. 112 078702 (2014) [2] M. Palus, M. Vejmelka, Phys. Rev. E 75, 056211 (2007) [3] N. Jajcay, J. Hlinka, S. Kravtsov, A. A. Tsonis, M. Palus, Time

  5. Pattern formations in miscellaneous mixtures of Bose-Einstein condensates and the higher-dimensional time-gated Manakov system

    SciTech Connect

    Kuetche, Victor K.; Bouetou, Thomas B.; Kofane, Timoleon C.; Moubissi, Alain B.; Porsezian, K.

    2010-11-15

    In this article, we investigate the structure and dynamics of miscellaneous mixtures of Bose-Einstein condensates confined within a time-independent anisotropic parabolic trap potential. In the zero-temperature mean-field approximation leading to coupled Gross-Pitaevskii equations for the macroscopic wave functions of the condensates, we show that these equations can be mapped onto the higher-dimensional time-gated Manakov system up to a first-order of accuracy. Paying particular attention to two-species mixtures and looking forward deriving a panel of miscellaneous excitations to the above equations, we analyze the singularity structure of the system by means of Weiss et al.'s [J. Weiss, M. Tabor, and G. Carnevale, J. Math. Phys. 24, 522 (1983); 25, 13 (1984).] methodology and provide its general Lax representation. As a result, we unearth a typical spectrum of localized and periodic coherent patterns while depicting elastic and nonelastic interactions among such structures alongside the splitting and resonance phenomena occurring during their motion.

  6. Energy-momentum conserving higher-order time integration of nonlinear dynamics of finite elastic fiber-reinforced continua

    NASA Astrophysics Data System (ADS)

    Erler, Norbert; Groß, Michael

    2015-05-01

    Since many years the relevance of fibre-reinforced polymers is steadily increasing in fields of engineering, especially in aircraft and automotive industry. Due to the high strength in fibre direction, but the possibility of lightweight construction, these composites replace more and more traditional materials as metals. Fibre-reinforced polymers are often manufactured from glass or carbon fibres as attachment parts or from steel or nylon cord as force transmission parts. Attachment parts are mostly subjected to small strains, but force transmission parts usually suffer large deformations in at least one direction. Here, a geometrically nonlinear formulation is necessary. Typical examples are helicopter rotor blades, where the fibres have the function to stabilize the structure in order to counteract large centrifugal forces. For long-run analyses of rotor blade deformations, we have to apply numerically stable time integrators for anisotropic materials. This paper presents higher-order accurate and numerically stable time stepping schemes for nonlinear elastic fibre-reinforced continua with anisotropic stress behaviour.

  7. Real-time evaluation of individual cow milk for higher cheese-milk quality with increased cheese yield.

    PubMed

    Katz, G; Merin, U; Bezman, D; Lavie, S; Lemberskiy-Kuzin, L; Leitner, G

    2016-06-01

    Cheese was produced in a series of experiments from milk separated in real time during milking by using the Afilab MCS milk classification service (Afikim, Israel), which is installed on the milk line in every stall and sorts milk in real time into 2 target tanks: the A tank for cheese production (CM) and the B tank for fluid milk products (FM). The cheese milk was prepared in varying ratios ranging from ~10:90 to ~90:10 CM:FM by using this system. Cheese was made with corrected protein-to-fat ratio and without it, as well as from milk stored at 4°C for 1, 2, 3, 4, and 8d before production. Cheese weight at 24h increased along the separation cutoff level with no difference in moisture, and dry matter increased. The data compiled allowed a theoretical calculation of cheese yield and comparing it to the original van Slyke equation. Whenever the value of Afi-Cf, which is the optical measure of curd firmness obtained by the Afilab instrument, was used, a better predicted level of cheese yield was obtained. In addition, 27 bulk milk tanks with milk separated at a 50:50 CM:FM ratio resulted in cheese with a significantly higher fat and protein, dry matter, and weight at 24h. Moreover, solids incorporated from the milk into the cheese were significantly higher in cheeses made of milk from A tanks. The influence of storage of milk up to 8d before cheese making was tested. Gross milk composition did not change and no differences were found in cheese moisture, but dry matter and protein incorporated in the cheese dropped significantly along the storage time. These findings confirm that milk stored for several days before processing is prone to physico-chemical deterioration processes, which result in loss of milk constituents to the whey and therefore reduced product yield. The study demonstrates that introducing the unknown parameters for calculating the predicted cheese yield, such as the empiric measured Afi-Cf properties, are more accurate and the increase in cheese

  8. Three-dimensional superhydrophobic copper 7,7,8,8-tetracyanoquinodimethane biointerfaces with the capability of high adhesion of osteoblasts

    NASA Astrophysics Data System (ADS)

    Zhou, Jie; Fan, Jun-Bing; Nie, Qiong; Wang, Shutao

    2016-02-01

    A three-dimensional superhydrophobic copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) nanowire array with the capability of high adhesion of osteoblasts was demonstrated. The CuTCNQ nanowire array was constructed by using a combined vapor deposition technique. The superhydrophobic nanowire array exhibited very high adhesion of osteoblasts, indicating that the CuTCNQ nanowire array was a good biointerface.A three-dimensional superhydrophobic copper 7,7,8,8-tetracyanoquinodimethane (CuTCNQ) nanowire array with the capability of high adhesion of osteoblasts was demonstrated. The CuTCNQ nanowire array was constructed by using a combined vapor deposition technique. The superhydrophobic nanowire array exhibited very high adhesion of osteoblasts, indicating that the CuTCNQ nanowire array was a good biointerface. Electronic supplementary information (ESI) available: Experimental details, the EDX, TEM, SAED and cell viability. See DOI: 10.1039/c5nr08305b

  9. Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture.

    PubMed

    Silkworth, J B; Cutler, D S; O'Keefe, P W; Lipinskas, T

    1993-04-01

    There is increasing need to understand the toxicity of complex environmental mixtures. The organic phase of a leachate (OPL) from the Love Canal chemical dump site is a complex mixture that contains over 100 organic compounds, including 0.74 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice congenic at the Ah locus were used to evaluate several toxic effects of the OPL, including immune function and hepatic enzyme induction. OPL toxicity was compared with that of pure TCDD in both C57BL/6J Ahb/b and congenic C57BL/6 Ahd/d (B6.D2) mice. Mice were given single oral doses of up to 2 g OPL/kg or 100 micrograms TCDD/kg, immunized, and evaluated after 7 days. The TCDD equivalent of the OPL was determined to be 3.9 and 5.0 ppm in C57BL/6J and B6.D2 mice, respectively. This is six times the TCDD content. The Ah phenotype-dependent response ratio was calculated by dividing the dose required to cause an effect in the B6.D2 strain by the dose causing the same effect in the C57BL/6J strain. Ratios based on both ED50s and the lowest observed adverse effect levels were used to determine whether each adverse effect was Ah phenotype-dependent, the extent to which TCDD contributed to the effect, whether there were interactive effects between the AhR ligands and nonligands and if they were additive, antagonistic, or synergistic, and whether the response was predictable based on the known chemical composition of the mixture. It was concluded that the non-TCDD component potentiated TCDD immune suppression, and possibly thymic atrophy, through AhR mechanisms. In contrast, this analysis indicated that the non-TCDD component of the OPL antagonized the ability of the TCDD component to induce hepatic AHH activity whereas OPL hepatomegaly was caused primarily by the non-TCDD component of the OPL. This study demonstrates that the toxicity of mixtures containing TCDD may not be accurately predicted based on the TCDD content alone and that this approach could be useful in the toxicologic

  10. Possible Interactions between the 2012 Mw 7.8 Haida Gwaii Subduction Earthquake and the Transform Queen Charlotte Fault

    NASA Astrophysics Data System (ADS)

    Hobbs, T. E.; Cassidy, J. F.; Dosso, S. E.

    2014-12-01

    This paper examines the effect of the October 2012 Mw 7.8 Haida Gwaii earthquake on aftershock nodal planes and the neighboring Queen Charlotte Fault (QCF) through Coulomb modeling and directivity analysis. The Haida Gwaii earthquake was the largest thrust event recorded in this region and ruptured an area of ~150 by 40 km on a gently NE-dipping fault off the west coast of Moresby Island, British Columbia. It is particularly interesting as it is located just to the west of the QCF, the predominantly right-lateral strike-slip fault separating the Pacific and North American plates. The QCF was the site of the largest recorded earthquake in Canada: the 1949 Ms 8.1 strike-slip earthquake whose rupture extended as far south as this 2012 event and roughly as far north as an Mw7.5 strike slip event at Craig, Alaska, which occurred just two months later in January 2013. The 75 km long portion of the QCF south of the 1949 rupture has not had a large (M ≥ 7) earthquake in over 116 years, representing a significant seismic gap. Coulomb stress transfer analysis is performed using finite fault models which incorporate seismic and geodetic data. Static stress changes are projected onto aftershock nodal planes and the QCF, including an inferred southern seismic gap. We find up to 86% of aftershocks are consistent with triggering, and as high as 96% for normal faulting events. The QCF experiences static stress changes greater than the empirically-determined threshold for triggering, with positive stress changes predicted for roughly half of the seismic gap region. Added stress from the mainshock and a lack of post-mainshock events make this seismic gap a likely location for future earthquakes. Empirical Green's function and directivity analyses are also performed to constrain rupture kinematics of the mainshock using systematic azimuthal variations in relative source time functions. Results indicate rupture progressed mainly to the northwest within 15o of the direction of the

  11. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    SciTech Connect

    Fullerton, Aaron M.; Roth, Robert A.; Ganey, Patricia E.

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  12. A novel Fast Gas Chromatography based technique for higher time resolution measurements of speciated monoterpenes in air

    NASA Astrophysics Data System (ADS)

    Jones, C. E.; Kato, S.; Nakashima, Y.; Kajii, Y.

    2013-12-01

    Biogenic emissions supply the largest fraction of non-methane volatile organic compounds (VOC) from the biosphere to the atmospheric boundary layer, and typically comprise a complex mixture of reactive terpenes. Due to this chemical complexity, achieving comprehensive measurements of biogenic VOC (BVOC) in air within a satisfactory time resolution is analytically challenging. To address this, we have developed a novel, fully automated Fast Gas Chromatography (Fast-GC) based technique to provide higher time resolution monitoring of monoterpenes (and selected other C9-C15 terpenes) during plant emission studies and in ambient air. To our knowledge, this is the first study to apply a Fast-GC based separation technique to achieve quantification of terpenes in air. Three chromatography methods have been developed for atmospheric terpene analysis under different sampling scenarios. Each method facilitates chromatographic separation of selected BVOC within a significantly reduced analysis time compared to conventional GC methods, whilst maintaining the ability to quantify individual monoterpene structural isomers. Using this approach, the C10-C15 BVOC composition of single plant emissions may be characterised within a ~ 14 min analysis time. Moreover, in situ quantification of 12 monoterpenes in unpolluted ambient air may be achieved within an ~ 11 min chromatographic separation time (increasing to ~ 19 min when simultaneous quantification of multiple oxygenated C9-C10 terpenoids is required, and/or when concentrations of anthropogenic VOC are significant). This corresponds to a two- to fivefold increase in measurement frequency compared to conventional GC methods. Here we outline the technical details and analytical capability of this chromatographic approach, and present the first in situ Fast-GC observations of 6 monoterpenes and the oxygenated BVOC linalool in ambient air. During this field deployment within a suburban forest ~ 30 km west of central Tokyo, Japan, the

  13. Spatial and temporal rupture process of the January 26, 2001, Gujarat, India, M S=7.8 earthquake

    NASA Astrophysics Data System (ADS)

    Xu, Li-Sheng; Chen, Yun-Tai; Gao, Meng-Tan

    2002-09-01

    The source parameters, such as moment tensor, focal mechanism, source time function (STF) and temporal-spatial rupture process, were obtained for the January 26, 2001, India, M S=7.8 earthquake by inverting waveform data of 27 GDSN stations with epicentral distances less than 90°. Firstly, combining the moment tensor inversion, the spatial distribution of intensity, disaster and aftershocks and the orientation of the fault where the earthquake lies, the strike, dip and rake of the seismogenic fault were determined to be 92°, 58° and 62°, respectively. That is, this earthquake was a mainly thrust faulting with the strike of near west-east and the dipping direction to south. The seismic moment released was 3.5×1020 Nm, accordingly, the moment magnitude M W was calculated to be 7.6. And then, 27 P-STFs, 22 S-STFs and the averaged STFs of them were determined respectively using the technique of spectra division in frequency domain and the synthetic seismogram as Green’s functions. The analysis of the STFs suggested that the earthquake was a continuous event with the duration time of 19 s, starting rapidly and ending slowly. Finally, the temporal-spatial distribution of the slip on the fault plane was imaged from the obtained P-STFs and S-STFs using an time domain inversion technique. The maximum slip amplitude on the fault plane was about 7 m. The maximum stress drop was 30 MPa, and the average one over the whole rupture area was 7 MPa. The rupture area was about 85 km long in the strike direction and about 60 km wide in the down-dip direction, which, equally, was 51 km deep in the depth direction. The rupture propagated 50 km eastwards and 35 km westwards. The main portion of the rupture area, which has the slip amplitude greater than 0.5 m, was of the shape of an ellipse, its major axis oriented in the slip direction of the fault, which indicated that the rupture propagation direction was in accordance with the fault slip direction. This phenomenon is popular

  14. Towards configurationally stable [4]helicenes: enantioselective synthesis of 12-substituted 7,8-dihydro[4]helicene quinones.

    PubMed

    Carreño, M Carmen; Enríquez, Alvaro; García-Cerrada, Susana; Sanz-Cuesta, M Jesús; Urbano, Antonio; Maseras, Feliu; Nonell-Canals, Alfons

    2008-01-01

    The synthesis of enantiopure C-12 methoxy- or alkyl-substituted 5,7,8,12b-tetrahydro[4]helicene quinones 16 and 17 and the 7,8-dihydroaromatic analogues 4 and 5 has been achieved from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone. In the first series, with a structure containing both central and helical chiralities, the R absolute configuration of the stereogenic carbon atom was defined after the asymmetric cycloaddition step, whereas the P or M helicity was shown to be dependent on the nature of the C-12 substituent. The size of this group was also defining the configurational stability of the final (P)-7,8-dihydro[4]helicene quinones 4 and 5. The interconversion barriers between the P and M helimers in the latter, computed with a DFT B3LYP method, matched well with the experimentally observed stability. Our study provided evidence that, in addition to steric effects, a small but significant role of electronic effects is governing the configurational stability of such helical quinones.

  15. Assessments of higher-order ionospheric effects on GPS coordinate time series: A case study of CMONOC with longer time series

    NASA Astrophysics Data System (ADS)

    Jiang, Weiping; Deng, Liansheng; Zhou, Xiaohui; Ma, Yifang

    2014-05-01

    Higher-order ionospheric (HIO) corrections are proposed to become a standard part for precise GPS data analysis. For this study, we deeply investigate the impacts of the HIO corrections on the coordinate time series by implementing re-processing of the GPS data from Crustal Movement Observation Network of China (CMONOC). Nearly 13 year data are used in our three processing runs: (a) run NO, without HOI corrections, (b) run IG, both second- and third-order corrections are modeled using the International Geomagnetic Reference Field 11 (IGRF11) to model the magnetic field, (c) run ID, the same with IG but dipole magnetic model are applied. Both spectral analysis and noise analysis are adopted to investigate these effects. Results show that for CMONOC stations, HIO corrections are found to have brought an overall improvement. After the corrections are applied, the noise amplitudes decrease, with the white noise amplitudes showing a more remarkable variation. Low-latitude sites are more affected. For different coordinate components, the impacts vary. The results of an analysis of stacked periodograms show that there is a good match between the seasonal amplitudes and the HOI corrections, and the observed variations in the coordinate time series are related to HOI effects. HOI delays partially explain the seasonal amplitudes in the coordinate time series, especially for the U component. The annual amplitudes for all components are decreased for over one-half of the selected CMONOC sites. Additionally, the semi-annual amplitudes for the sites are much more strongly affected by the corrections. However, when diplole model is used, the results are not as optimistic as IGRF model. Analysis of dipole model indicate that HIO delay lead to the increase of noise amplitudes, and that HIO delays with dipole model can generate false periodic signals. When dipole model are used in modeling HIO terms, larger residual and noise are brought in rather than the effective improvements.

  16. Toxic assessment of PCBs by the 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent in common cormorant (Phalacrocorax carbo) from Japan.

    PubMed

    Guruge, K S; Tanabe, S; Fukuda, M

    2000-05-01

    Common cormorants collected from three colonies and their fish diet were analyzed for PCB congeners and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) were estimated. The highest total PCBs (40 microg/g wet weight) found in adult cormorants from Shinobazu Pond located in Central Tokyo, was sevenfold higher than that from Lake Biwa. IUPAC 153 was the most abundant congener in adults and eggs, whereas IUPAC 28 + 31 was higher in some chicks and exhibited growth-related congeneric enrichment. The estimated metabolic index (MI) for PCB congeners revealed that monoand non-ortho coplanars had higher bioaccumulation in cormorant liver and were expected to cause toxic effects. Among non-ortho coplanars, IUPAC 126 was predominant, and total non-ortho coplanars and TEQs in cormorants were threefold higher in Shinobazu Pond than those from Lake Biwa. The non-ortho IUPAC 126 contributed a higher portion to the total TEQs followed by IUPAC 105 and IUPAC 77. The hepatic IUPAC 169/126 ratio increased significantly with TEQs, implying a potential induction of drug-metabolizing enzymes in Shinobazu Pond cormorants. Based on the available data, PCB contamination in cormorants is enough to pose sublethal effects, especially in Shinobazu Pond and Godaiba Island, Tokyo, Japan. This could be a reason for recently observed high chick and juvenile mortality in those colonies in Tokyo.

  17. Determination of ( sup 3 H)-2,3,7,8-tetrachlorodibenzo-p-dioxin in human feces to ascertain its relative metabolism in man

    SciTech Connect

    Wendling, J.M.; Orth, R.G.; Poiger, H. )

    1990-04-15

    Human feces samples from a self-dosing experiment were analyzed by gas chromatography/mass spectrometry (GC/MS) for ({sup 3}H)-2,3,7,8-tetrachlorodibenzo-p-dioxin ({sup 3}H-2378-TCDD) to determine that 36-44% of the radioactivity was attributable to the parent compound. This method, using isotope dilution analysis, proved to be difficult due to the unexpectedly higher native 2378-TCDD background which created abnormally large precision ranges around the calculated feces concentrations of 0.1-0.2 pg/g. These results were supported by additional analyses involving the GC/MS chemical cleanup method combined with liquid scintillation counting which showed that at most, 50% of the radioactivity was due to 2378-TCDD metabolites resulting in a minimum metabolism of 50% for these samples.

  18. Intelligent control and adaptive systems; Proceedings of the Meeting, Philadelphia, PA, Nov. 7, 8, 1989

    NASA Technical Reports Server (NTRS)

    Rodriguez, Guillermo (Editor)

    1990-01-01

    Various papers on intelligent control and adaptive systems are presented. Individual topics addressed include: control architecture for a Mars walking vehicle, representation for error detection and recovery in robot task plans, real-time operating system for robots, execution monitoring of a mobile robot system, statistical mechanics models for motion and force planning, global kinematics for manipulator planning and control, exploration of unknown mechanical assemblies through manipulation, low-level representations for robot vision, harmonic functions for robot path construction, simulation of dual behavior of an autonomous system. Also discussed are: control framework for hand-arm coordination, neural network approach to multivehicle navigation, electronic neural networks for global optimization, neural network for L1 norm linear regression, planning for assembly with robot hands, neural networks in dynamical systems, control design with iterative learning, improved fuzzy process control of spacecraft autonomous rendezvous using a genetic algorithm.

  19. Evaluation of toxicological biomarkers in secreted proteins of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and their expressions in the plasma of rats and incineration workers.

    PubMed

    Phark, Sohee; Park, So-Young; Chang, Yoon-Seok; Choi, Seonyoung; Lim, Ji-youn; Kim, Yoonjin; Seo, Jong Bok; Jung, Woon-Won; Sul, Donggeun

    2016-05-01

    Toxicological biomarkers of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) were investigated in proteins secreted by HepG2 cells and their expression levels were determined in the plasma of rats exposed to 2,3,7,8-TCDD and in the plasma of incineration workers exposed to dioxins. HepG2 cells were treated with various concentrations of 2,3,7,8-TCDD (0, 0.25, 0.5, 1, 2.5, 5, 10, 25 nM) for 24 or 48 h. MTT and Comet assays were performed to determine cytotoxicities and genotoxicities to select exposure concentrations for the proteomic analysis of proteins secreted by 2,3,7,8-TCDD-treated cells. In the proteomic analysis, dose- and time-dependent toxicological biomarkers were evaluated using two pI ranges (4-7 and 6-9) using a large gel 2-DE system. Fifteen secreted proteins were identified by a nano-LC-ESI-MS/MS and nano-ESI on a Q-TOF2 MS and the identities of eight secreted proteins including glyoxalase 1 (GLO 1), homogentisate dioxygenase (HGD), peroxiredoxin 1 (PRX 1), proteasome subunit beta type (PSMB) 5 and 6, UDP-glucose 6-dehydrogenase (UDP-GlcDH), hydroxyacyl-coenzyme A dehydrogenase (HADH) and serotransferrin (STF) were confirmed by western blotting. Of these, PSMB 5 and PRX 1 were also found in the plasma of rats exposed to 2,3,7,8-TCDD, whereas GLO 1, HGD, PSMB 6 and PRX 1 were found in the plasma of incineration workers exposed to dioxins.

  20. Analysis of the tsunami generated by the MW 7.8 1906 San Francisco earthquake

    USGS Publications Warehouse

    Geist, E.L.; Zoback, M.L.

    1999-01-01

    We examine possible sources of a small tsunami produced by the 1906 San Francisco earthquake, recorded at a single tide gauge station situated at the opening to San Francisco Bay. Coseismic vertical displacement fields were calculated using elastic dislocation theory for geodetically constrained horizontal slip along a variety of offshore fault geometries. Propagation of the ensuing tsunami was calculated using a shallow-water hydrodynamic model that takes into account the effects of bottom friction. The observed amplitude and negative pulse of the first arrival are shown to be inconsistent with small vertical displacements (~4-6 cm) arising from pure horizontal slip along a continuous right bend in the San Andreas fault offshore. The primary source region of the tsunami was most likely a recently recognized 3 km right step in the San Andreas fault that is also the probable epicentral region for the 1906 earthquake. Tsunami models that include the 3 km right step with pure horizontal slip match the arrival time of the tsunami, but underestimate the amplitude of the negative first-arrival pulse. Both the amplitude and time of the first arrival are adequately matched by using a rupture geometry similar to that defined for the 1995 MW (moment magnitude) 6.9 Kobe earthquake: i.e., fault segments dipping toward each other within the stepover region (83??dip, intersecting at 10 km depth) and a small component of slip in the dip direction (rake=-172??). Analysis of the tsunami provides confirming evidence that the 1906 San Francisco earthquake initiated at a right step in a right-lateral fault and propagated bilaterally, suggesting a rupture initiation mechanism similar to that for the 1995 Kobe earthquake.

  1. Study of Interpolated Timing Recovery Phase-Locked Loop with Linearly Constrained Adaptive Prefilter for Higher-Density Optical Disc

    NASA Astrophysics Data System (ADS)

    Kajiwara, Yoshiyuki; Shiraishi, Junya; Kobayashi, Shoei; Yamagami, Tamotsu

    2009-03-01

    A digital phase-locked loop (PLL) with a linearly constrained adaptive filter (LCAF) has been studied for higher-linear-density optical discs. LCAF has been implemented before an interpolated timing recovery (ITR) PLL unit in order to improve the quality of phase error calculation by using an adaptively equalized partial response (PR) signal. Coefficient update of an asynchronous sampled adaptive FIR filter with a least-mean-square (LMS) algorithm has been constrained by a projection matrix in order to suppress the phase shift of the tap coefficients of the adaptive filter. We have developed projection matrices that are suitable for Blu-ray disc (BD) drive systems by numerical simulation. Results have shown the properties of the projection matrices. Then, we have designed the read channel system of the ITR PLL with an LCAF model on the FPGA board for experiments. Results have shown that the LCAF improves the tilt margins of 30 gigabytes (GB) recordable BD (BD-R) and 33 GB BD read-only memory (BD-ROM) with a sufficient LMS adaptation stability.

  2. Dystonia and tremor following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Klawans, H.L.

    1987-01-01

    Forty-seven railroad workers who were exposed to polychlorinated phenols, including dioxin (TCDD), during 1979 while cleaning up the chemical spillage following damage to a tank car filled with these chemicals were followed medically for the subsequent 6 years. Two committed suicide. The initial neurological complaints included a sense of fatigue and muscle aching, both of which have been reported in other individuals following dioxin exposure. On detailed neurological examination in December, 1985, 24 of 45 had dystonic writer's cramp and/or other action dystonias of the hands. None of the involved individuals had a family history of dystonia, and all 24 dated the onset of the dystonia to the first 2 to 3 years subsequent to their toxic exposure. The dystonias varied in severity but were usually mild. No other types of dystonic involvement were recognized. Thirty-five of the 45 individuals also manifested postural and terminal intention tremor which resembled benign essential tremor. None of the involved individuals had a family history of tremor, and all 35 of those affected dated the onset of the tremor to some time subsequent to their toxic exposure. Forty-three of 45 patients had histories and findings suggestive of peripheral neuropathy. This is the first report relating any type of dystonia to prior dioxin exposure and the first report relating action dystonia, such as dystonic writer's cramp, and postural/terminal intention tremor, to toxic exposure of any type.

  3. Developmental and posthatch effects of in ovo exposure to 2,3,7,8-TCDD, 2,3,4,7,8-PECDF, and 2,3,7,8-TCDF in Japanese quail (Coturnix japonica), common pheasant (Phasianus colchicus), and white leghorn chicken (Gallus gallus domesticus) embryos.

    PubMed

    Cohen-Barnhouse, Andrew M; Zwiernik, Matthew J; Link, Jane E; Fitzgerald, Scott D; Kennedy, Sean W; Giesy, John P; Wiseman, Steve; Jones, Paul D; Newsted, John L; Kay, Denise; Bursian, Steven J

    2011-07-01

    An egg injection study was conducted to confirm a proposed model of relative sensitivity of three avian species to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like chemicals. It was previously reported that the order of species sensitivity to in ovo exposure to TCDD, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or 2,3,7,8-tetrachlorodibenzofuran (TCDF) at doses ranging from 0.044 to 37 picomoles (pmol)/g egg was the chicken (Gallus gallus domesticus), common pheasant (Phasianus colchicus), and Japanese quail (Coturnix japonica) based on embryo mortality and hepatic enzyme induction. In the present study, the incidence of developmental deformities, changes in body and relative organ masses, and organ pathology of hatchlings as additional indicators of species sensitivity were assessed; in addition, embryo mortality in the three species was categorized by stage of development. Embryo mortality varied temporally with significant increases generally occurring after organogenesis and just prior to hatching. A significant increase in the percentage of developmental deformities was observed only in Japanese quail exposed to TCDF. Body and relative organ masses of quail, pheasants, and chickens dosed in ovo with TCDD, PeCDF, or TCDF were not consistently affected. Chemical-related pathology occurred only in livers of quail at the greatest doses of each compound. These results indicated that the incidence of developmental deformities, changes in body and relative organ masses and organ pathology could not be used as indicators of species sensitivity or chemical potency.

  4. EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ...

    EPA Pesticide Factsheets

    While the effect that TCDD has on humoral immunity in the mouse has been well documented, it has not been for the rat. n this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. ice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 ug/kg, 7 days prior to intravenous immunization with SRBC. our days later the PFC response to SRBC was determined. ice showed a dose related suppression of the PFC response, with an ED50 of 0.71 ug/kg TCDD. n contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 ug/kg. he inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 ug/kg TCDD, respectively. here was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. henotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10 or 30 ug/kg) and SREC-immunized mice and rats revealed that CD4-CD8+ splenocytes were reduced in a dose related manner in rats only and that this reduction in CD4-CD8+ was accompanied by a dose related increase in IgM+ splenocytes. hese results demonstrate species differences in the effect of TCDD on the PFC response to SRBC w

  5. 2,3,4,7,8-Pentachlorodibenzofuran is far less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin in disrupting the pituitary–gonad axis of the rat fetus

    SciTech Connect

    Taura, Junki; Takeda, Tomoki; Fujii, Misaki; Hattori, Yukiko; Ishii, Yuji; Kuroki, Hiroaki; Tsukimori, Kiyomi; Uchi, Hiroshi; Furue, Masutaka; Yamada, Hideyuki

    2014-11-15

    The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary–gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect. While PnCDF, at a dose sufficient to cause a reduction in fetal LH, provoked defects in sexual behavior at adulthood, a dose less than the ED{sub 50} failed to produce any abnormality. There was a loss of fetal body weight following in utero exposure to PnCDF, and the effect of PnCDF was also much less than that of TCDD. The disturbance in fetal growth was suggested to be due to a reduction in the level of fetal growth hormone (GH) by dioxins. The disorder caused by PnCDF/TCDD in the fetal pituitary–gonad axis occurred at doses less than those needed to cause wasting syndrome in pubertal rats. The harmful effect of PnCDF relative to TCDD was more pronounced in fetal rats than in pubertal rats. These lines of evidence suggest that: 1) PnCDF as well as TCDD imprints defects in sexual behavior by disrupting the fetal pituitary–gonad axis; 2) these dioxins hinder fetal growth by reducing the expression of fetal GH; and 3) the fetal effects of PnCDF/TCDD are more sensitive than sub-acute toxicity during puberty, and the relative effect of PnCDF varies markedly depending on the indices used. - Highlights: • 2,3,4,7,8-Pentachlorodibenzofuran (PnCDF) lowers gonadal steroidogenesis in fetuses. • PnCDF exerts the above effect through an initial attenuation in gonadotropin level. • PnCDF imprints sexual immaturity by transiently disrupting the pituitary–gonad axis. • PnCDF also disturbs pup growth probably due to a reduction in growth hormone level. • The above effects are far lesser in PnCDF than 2,3,7,8

  6. The tissue distribution of 2,3,7,8-chlorine substituted dibenzo-p-dioxins in humans who died of cancer

    SciTech Connect

    Muto, Hajime; Shinada, Masayuki; Abe, Touru; Takizawa, Yukio )

    1991-01-01

    The tissue distribution of 2,3,7,8-chlorine substituted dibenzo-p-dioxins was conducted in 11 patients who died of cancer. The concentration of octachlorodibenzo-p-dioxin(octa-CDD) was the highest in each organ and tissue and hepta-CDD was also found at relatively high levels, second only to OCDD. The levels of 1,2,3,7,8-penta-CDD and 1,2,3,6,7,8-hexa-CDD in the spleen were the highest, respectively. 2,3,7,8-Tetra-CDD was also detected and its concentration was the highest in the gonad. From the 2,3,7,8-TCDD toxic equivalent calculations, the highest equivalent value was obtained from a 54-year-old female who died of cancerous goiter. This individual had the highest concentrations of 2,3,7,8-substituted penta- and hexa-CDDs among the 11 patients.

  7. Higher Urinary Lignan Concentrations in Women but Not Men Are Positively Associated with Shorter Time to Pregnancy1234

    PubMed Central

    Mumford, Sunni L.; Sundaram, Rajeshwari; Schisterman, Enrique F.; Sweeney, Anne M.; Barr, Dana Boyd; Rybak, Michael E.; Maisog, Jose M.; Parker, Daniel L.; Pfeiffer, Christine M.; Louis, Germaine M. Buck

    2014-01-01

    Phytoestrogens have been associated with subtle hormonal changes, although effects on fecundity are unknown. Our objective was to evaluate the association between male and female urinary phytoestrogen (isoflavone and lignan) concentrations and time to pregnancy (TTP) in a population-based cohort of 501 couples desiring pregnancy and discontinuing contraception. Couples were followed for 12 mo or until pregnancy. Fecundability ORs (FORs) and 95% CIs were estimated after adjusting for age, body mass index, race, site, creatinine, supplement use, and physical activity in relation to female, male, and joint couple concentrations. Models included the phytoestrogen of interest and the sum of the remaining individual phytoestrogens. FORs <1 denote a longer TTP and FORs >1 a shorter TTP. Urinary lignan concentrations were higher, on average, among female partners of couples who became pregnant during the study compared with women who did not become pregnant (median enterodiol: 118 vs. 80 nmol/L; P < 0.10; median enterolactone: 990 vs. 412 nmol/L; P < 0.05) and were associated with significantly shorter TTP in models based on both individual and couples’ concentrations (couples' models: enterodiol FOR, 1.13; 95% CI: 1.02, 1.26; enterolactone FOR, 1.11; 95% CI: 1.01, 1.21). Male lignan concentrations were not associated with TTP, nor were isoflavone concentrations. Sensitivity analyses showed that associations observed are unlikely to be explained by potential unmeasured confounding by lifestyle or other nutrients. Our results suggest that female urinary lignan concentrations at levels characteristic of the U.S. population are associated with a shorter TTP among couples who are attempting to conceive, highlighting the importance of dietary influences on fecundity. PMID:24401816

  8. Biochemical and Biophysical Investigation of the Brain-derived Neurotrophic Factor Mimetic 7,8-Dihydroxyflavone in the Binding and Activation of the TrkB Receptor*

    PubMed Central

    Liu, Xia; Obianyo, Obiamaka; Chan, Chi Bun; Huang, Junjian; Xue, Shenghui; Yang, Jenny J.; Zeng, Fanxing; Goodman, Mark; Ye, Keqiang

    2014-01-01

    7,8-dihydroxyflavone (7,8-DHF), a newly identified small molecular TrkB receptor agonist, rapidly activates TrkB in both primary neurons and the rodent brain and mimics the physiological functions of the cognate ligand BDNF. Accumulating evidence supports that 7,8-DHF exerts neurotrophic effects in a TrkB-dependent manner. Nonetheless, the differences between 7,8-DHF and BDNF in activating TrkB remain incompletely understood. Here we show that 7,8-DHF and BDNF exhibit different TrkB activation kinetics in which TrkB maturation may be implicated. Employing two independent biophysical approaches, we confirm that 7,8-DHF interacts robustly with the TrkB extracellular domain, with a Kd of ∼10 nm. Although BDNF transiently activates TrkB, leading to receptor internalization and ubiquitination/degradation, in contrast, 7,8-DHF-triggered TrkB phosphorylation lasts for hours, and the internalized receptors are not degraded. Notably, primary neuronal maturation may be required for 7,8-DHF but not for BDNF to elicit the full spectrum of TrkB signaling cascades. Hence, 7,8-DHF interacts robustly with the TrkB receptor, and its agonistic effect may be mediated by neuronal development and maturation. PMID:25143381

  9. Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor.

    PubMed

    Liu, Xia; Obianyo, Obiamaka; Chan, Chi Bun; Huang, Junjian; Xue, Shenghui; Yang, Jenny J; Zeng, Fanxing; Goodman, Mark; Ye, Keqiang

    2014-10-03

    7,8-dihydroxyflavone (7,8-DHF), a newly identified small molecular TrkB receptor agonist, rapidly activates TrkB in both primary neurons and the rodent brain and mimics the physiological functions of the cognate ligand BDNF. Accumulating evidence supports that 7,8-DHF exerts neurotrophic effects in a TrkB-dependent manner. Nonetheless, the differences between 7,8-DHF and BDNF in activating TrkB remain incompletely understood. Here we show that 7,8-DHF and BDNF exhibit different TrkB activation kinetics in which TrkB maturation may be implicated. Employing two independent biophysical approaches, we confirm that 7,8-DHF interacts robustly with the TrkB extracellular domain, with a Kd of ∼10 nm. Although BDNF transiently activates TrkB, leading to receptor internalization and ubiquitination/degradation, in contrast, 7,8-DHF-triggered TrkB phosphorylation lasts for hours, and the internalized receptors are not degraded. Notably, primary neuronal maturation may be required for 7,8-DHF but not for BDNF to elicit the full spectrum of TrkB signaling cascades. Hence, 7,8-DHF interacts robustly with the TrkB receptor, and its agonistic effect may be mediated by neuronal development and maturation.

  10. Higher Education in Russia: Traditions and Modern Times (Report at the Seventh Congress of the Russian Union of Rectors)

    ERIC Educational Resources Information Center

    Sadovnichii, V.

    2004-01-01

    This article represents a speech delivered by the author at the Seventh Congress of the Russian Union of Rectors. In his address, the author describes the current higher educational trend in Russia. He explains how higher education's orientation toward the state, its openness to all social classes, and its fundamental character are the principles…

  11. Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced immunotoxicity

    SciTech Connect

    Pazdernik, T.L.; Rozman, K.K.

    1985-02-18

    Radiothyroidectomy protected against 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD)-induced immunotoxicity in rats as assessed by the spleen anti-SRBC plaque-forming cell assay. Thyroxin (T/sub 4/) replacement therapy partially reversed the effects of thyroidectomy on T/sub 4/ and triiodothyronine (T/sub 3/) serum levels, body weight and immune function as well as restored TCDD-induced immunotoxicity. Thus, hypothyroidism induced by TCDD exposure can be viewed as a protective response of the organism to reduce the insult caused by TCDD.

  12. [Functional organization of the cerebral cortex during preparation to recognition of incomplete linedrawings in 7-8 years-old children and adults].

    PubMed

    Farber, D A; Machinskaia, R I; Kurganskiĭ, A V; Petrenko, N E

    2014-01-01

    Functional interaction between prefrontal, temporal and tempo-parieto-occipital zones during preparation to recognition of incomplete linedrawings were analyzed in adults (n = 26) and children of 7-8 years old (n = 20). The strength of cortico-cortical interactions was estimated with the imaginary part of the complex-valued coherence at the frequency of alpha-rhythm (Jα). The Jα value was analyzed in the following three experimental conditions which corresponded to different stages of preparation to visual recognition: nonspecific sustained attention in the period preceding the cue (C1); focused attention in the period preceding a not-yet-recognized target stimulus (C2) and focused attention prior the successfully recognized stimulus (C3). When sustained attention changed to focused attention toward a target stimulus Jα increased in adults but decreased in children. Comparing Jα in the subgroups of both adults and children that showed highest recognition scores helped to uncover the age-related pattern of rearrangement of the cortico-cortical functional interactions in alpha-rhythm. That pattern was found to be hemisphere-specific and different at different stages of preparation to recognition of incomplete linedrawings. In adults, the maximal Jα were found in the left hemisphere during the period preceding the recognition of a target stimulus. At this stage of the functional preparatory tuning, in adults, Jα in the left hemisphere was significantly greater than in children. In adults, Jα related to the right hemisphere attained the highest values when attention was directed to not-yet-recognized stimuli. These values were significantly higher than similar values measured in children. In children, Jα reached its highest value during sustained attention. The characteristic pattern of functional interactions among prefrontal, temporal and temporo-parieto-occipital cortices that observed in children of 7-8 years old during preparatory functional tuning for the

  13. A study of the effect of rotational mixing on massive stars evolution: surface abundances of Galactic O7-8 giant stars

    NASA Astrophysics Data System (ADS)

    Martins, F.; Simón-Díaz, S.; Barbá, R. H.; Gamen, R. C.; Ekström, S.

    2017-02-01

    Context. Massive star evolution remains only partly constrained. In particular, the exact role of rotation has been questioned by puzzling properties of OB stars in the Magellanic Clouds. Aims: Our goal is to study the relation between surface chemical composition and rotational velocity, and to test predictions of evolutionary models including rotation. Methods: We have performed a spectroscopic analysis of a sample of fifteen Galactic O7-8 giant stars. This sample is homogeneous in terms of mass, metallicity and evolutionary state. It is made of stars with a wide range of projected rotational velocities. Results: We show that the sample stars are located on the second half of the main sequence, in a relatively narrow mass range (25-40 M⊙). Almost all stars with projected rotational velocities above 100 km s-1 have N/C ratios about ten times the initial value. Below 100 km s-1 a wide range of N/C values is observed. The relation between N/C and surface gravity is well reproduced by various sets of models. Some evolutionary models including rotation are also able to consistently explain slowly rotating, highly enriched stars. This is due to differential rotation which efficiently transports nucleosynthesis products and allows the surface to rotate slower than the core. In addition, angular momentum removal by winds amplifies surface braking on the main sequence. Comparison of the surface composition of O7-8 giant stars with a sample of B stars with initial masses about four times smaller reveal that chemical enrichment scales with initial mass, as expected from theory. Conclusions: Although evolutionary models that include rotation face difficulties in explaining the chemical properties of O- and B-type stars at low metallicity, some of them can consistently account for the properties of main-sequence Galactic O stars in the mass range 25-40 M⊙.

  14. Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats.

    PubMed

    Ciftci, Osman; Vardi, Nigar; Ozdemir, Ilknur

    2013-03-01

    The objective of current study is to investigate the effects of the administration of chrysin (CH) and quercetin (Q) on rat liver in which oxidative and histological damage had been induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were randomly divided into six equal groups. TCDD was orally administered at the dose of 2 μg/kg/week, and Q and CH were orally administered at the doses of 20 mg/kg day and 50 mg/kg/day, respectively, by gavages dissolved in corn oil. The liver samples to be analyzed for the determination of oxidative and histological alternations were taken from rats at 60 days. The results indicated that although 2,3,7,8-TCDD significantly induced (P ≤ 0.01) lipid peroxidation (increase of MDA levels), it positively affected oxidant/antioxidant system (a decline in the levels of GSH, CAT, GSH-Px, and CuZn-SOD) in rats significantly. The histological changes observed in the liver correlated with the biochemical findings. However, these effects of TCDD on oxidative and histological changes were eliminated by Q and CH treatment. In conclusion, TCDD caused an adverse effect on rat's liver. When Q and CH were given together with TCDD, they prevented hepatotoxicty induced by TCDD. Thus, it is thought that Q and CH may be useful as a new category of anti-TCDD toxicity agent.

  15. Structural Characterization of the Mycobacterium tuberculosis Biotin Biosynthesis Enzymes 7,8-Diaminopelargonic Acid Synthase and Dethiobiotin Synthetase†,‡

    PubMed Central

    Dey, Sanghamitra; Lane, James M.; Lee, Richard E.; Rubin, Eric J.; Sacchettini, James C.

    2010-01-01

    Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 Å and 1.85 Å. Superimposition of the DAPAS structures bound either to the SAM analog sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 Å, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb. PMID:20565114

  16. Analysis of 7,8-Dihydro-8-oxo-2′-deoxyguanosine in Cellular DNA during Oxidative Stress

    PubMed Central

    2009-01-01

    Analysis of cellular 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dGuo) as a biomarker of oxidative DNA damage has been fraught with numerous methodological problems. This is primarily due to artifactual oxidation of dGuo that occurs during DNA isolation and hydrolysis. Therefore, it has become necessary to rely on using the comet assay, which is not necessarily specific for 8-oxo-dGuo. A highly specific and sensitive method based on immunoaffinity purification and stable isotope dilution liquid chromatography (LC)-multiple reaction monitoring (MRM)/mass spectrometry (MS) that avoids artifact formation has now been developed. Cellular DNA was isolated using cold DNAzol (a proprietary product that contains guanidine thiocyanate) instead of chaotropic- or phenol-based methodology. Chelex-treated buffers were used to prevent Fenton chemistry-mediated generation of reactive oxygen species (ROS) and artifactual oxidation of DNA bases. Deferoxamine was also added to all buffers in order to complex any residual transition metal ions remaining after Chelex treatment. The LC-MRM/MS method was used to determine that the basal 8-oxo-dGuo level in DNA from human bronchoalveolar H358 cells was 2.2 ± 0.4 8-oxo-dGuo/107 dGuo (mean ± standard deviation) or 5.5 ± 1.0 8-oxo-dGuo/108 nucleotides. Similar levels were observed in human lung adenocarcinoma A549 cells, mouse hepatoma Hepa-1c1c7 cells, and human HeLa cervical epithelial adenocarcinoma cells. These values are an order of magnitude lower than is typically reported for basal 8-oxo-dGuo levels in DNA as determined by other MS- or chromatography-based assays. H358 cells were treated with increasing concentrations of potassium bromate (KBrO3) as a positive control or with the methylating agent methyl methanesulfonate (MMS) as a negative control. A linear dose−response for 8-oxo-dGuo formation (r2 = 0.962) was obtained with increasing concentrations of KBrO3 in the range of 0.05 mM to 2.50 mM. In contrast, no 8-oxo-dGuo was

  17. Educational Family Background and the Realisation of Educational Career Intentions: Participation of German Upper Secondary Graduates in Higher Education over Time

    ERIC Educational Resources Information Center

    Weiss, Felix; Steininger, Hanna-Marei

    2013-01-01

    In this article, we evaluate the impact of social origin on the realisation of educational intentions at the time of becoming eligible for higher education in Germany. In general, we find high persistence of intentions and actual attendance of higher education. However, effects of parental education on the changes of educational intentions…

  18. Salaries, Tenure, and Fringe Benefits of Full-Time Instructional Faculty. Higher Education General Information Survey (HEGIS) [machine-readable data file].

    ERIC Educational Resources Information Center

    VSE Corp., Alexandria, VA.

    The "Faculty Salary Survey" machine-readable data file (MRDF) is one component of the Higher Education General Information Survey (HEGIS). It contains data about salaries, tenure, and fringe benefits for full-time instructional faculty from over 3,000 institutions of higher education located in the United States and its outlying areas.…

  19. CHARACTERIZATION OF STABLE BENZOLALPYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA AND POLYDEOXYNUCLEOTIDES

    EPA Science Inventory

    Bcnzo[a]pyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

  20. CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

    EPA Science Inventory

    Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

  1. LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

    EPA Science Inventory

    Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

  2. Effect of 7,8-dihydroneopterin mediated CD36 down regulation and oxidant scavenging on oxidised low-density lipoprotein induced cell death in human macrophages.

    PubMed

    Shchepetkina, Anastasia A; Hock, Barry D; Miller, Allison; Kennedy, Martin A; Gieseg, Steven P

    2017-03-26

    The role of CD36 in oxidised low-density lipoprotein (oxLDL) mediated cell death was examined by down regulating the receptor level with the macrophage generated antioxidant 7,8-dihydroneopterin. Down regulation of CD36 protein levels in human monocyte derived macrophages by 7,8-dihydroneopterin corresponded to a decrease in CD36-mRNA. The oxidation products of 7,8-dihydroneopterin, dihydroxanthopterin and neopterin did not significantly down regulate CD36. The CD36 down regulation resulted in a decrease in oxLDL uptake measured as 7-ketocholesterol accumulation. Though less oxLDL was taken up by the macrophages as a result of the 7,8-dihydroneopterin induced down regulation in CD36 levels, the cytotoxicity of the oxLDL was not decreased. Addition of 7,8-dihydroneopterin to oxLDL treated macrophages decreased the concentration of intracellular oxidants. In the presence of oxLDL, 7,8-dihydroneopterin was oxidised to neopterin showing that the 7,8-dihydroneopterin was scavenging intracellular oxidants generated in response to the oxLDL. The results show CD36 down regulation does not protect human macrophages form oxLDL cytotoxicity but 7,8-dihydroneopterin intracellular oxidant scavenging is protective.

  3. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS

    PubMed Central

    Crabtree, Mark J.; Smith, Caroline L.; Lam, George; Goligorsky, Michael S.; Gross, Steven S.

    2009-01-01

    5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs). Oxidation of BH4, in the setting of diabetes and other chronic vasoinflammatory conditions, can cause cofactor insufficiency and uncoupling of endothelial NOS (eNOS), manifest by a switch from nitric oxide (NO) to superoxide production. Here we tested the hypothesis that eNOS uncoupling is not simply a consequence of BH4 insufficiency, but rather results from a diminished ratio of BH4 vs. its catalytically incompetent oxidation product, 7,8-dihydrobiopterin (BH2). In support of this hypothesis, [3H]BH4 binding studies revealed that BH4 and BH2 bind eNOS with equal affinity (Kd ≈ 80 nM) and BH2 can rapidly and efficiently replace BH4 in preformed eNOS-BH4 complexes. Whereas the total biopterin pool of murine endothelial cells (ECs) was unaffected by 48-h exposure to diabetic glucose levels (30 mM), BH2 levels increased from undetectable to 40% of total biopterin. This BH2 accumulation was associated with diminished calcium ionophore-evoked NO activity and accelerated superoxide production. Since superoxide production was suppressed by NOS inhibitor treatment, eNOS was implicated as a principal superoxide source. Importantly, BH4 supplementation of ECs (in low and high glucose-containing media) revealed that calcium ionophore-evoked NO bioactivity correlates with intracellular BH4: BH2 and not absolute intracellular levels of BH4. Reciprocally, superoxide production was found to negatively correlate with intracellular BH4:BH2. Hyperglycemia-associated BH4 oxidation and NO insufficiency was recapitulated in vivo, in the Zucker diabetic fatty rat model of type 2 diabetes. Together, these findings implicate diminished intracellular BH4:BH2, rather than BH4 depletion per se, as the molecular trigger for NO insufficiency in diabetes. PMID:18192221

  4. A Call to Action on New England's Innovation Economy: Will Business and Higher Education Answer This Time?

    ERIC Educational Resources Information Center

    Guenther, William

    2003-01-01

    Mass Insight Corp, a public policy and communications firm that organizes public-private initiatives to support economic growth in Massachusetts, recently issued a new report, titled "An Economy at Risk," making the case for a Massachusetts economic development strategy organized around higher education and science and technology.…

  5. Australian Higher Education Leaders in Times of Change: The Role of Pro Vice-Chancellor and Deputy Vice-Chancellor

    ERIC Educational Resources Information Center

    Scott, Geoff; Bell, Sharon; Coates, Hamish; Grebennikov, Leonid

    2010-01-01

    This paper discusses responses provided by 31 Pro Vice-Chancellors (PVCs) and Deputy Vice-Chancellors (DVCs) who were part of a larger study of more than 500 higher education leaders in roles ranging from DVC to head of programme in 20 Australian universities. Using both quantitative and qualitative data the paper gives an insider's perspective on…

  6. A Lesson of Lost Political Capital in Public Higher Education: Leadership Challenges in a Time of Needed Organizational Change

    ERIC Educational Resources Information Center

    Hilton, Mark; Jacobson, Rod

    2012-01-01

    All higher education institutions are struggling with a rapidly changing market and financial landscape. Here is a management-centered analysis of what happened when a college president, recognizing the need to make a radical adaptation to those changes, tried moving a campus community to a new organizational model, without collegial consensus,…

  7. Breaking the Mold: New Approaches for Higher Education in Tough Economic Times. Complete to Compete Briefing Paper

    ERIC Educational Resources Information Center

    Carey, Kevin

    2011-01-01

    Human capital is the key to economic development. Without highly-skilled workers, states and territories cannot attract the productive businesses they need. That makes higher education a key element of any governor's growth strategy. But many public colleges and universities are struggling to produce more graduates. Overall graduation rates often…

  8. Funding System of Full-Time Higher Education and Technical Efficiency: Case of the University of Ljubljana

    ERIC Educational Resources Information Center

    Tajnikar, Maks; Debevec, Jasmina

    2008-01-01

    The present paper tackles the issue of the higher education funding system in Slovenia. Its main attribute is that institutions are classified into study groups according to their fields of education, and funds granted by the state are based on their weights or study group factors (SGF). Analysis conducted using data envelopment analysis tested…

  9. Applying the Modality Principle to Real-Time Feedback and the Acquisition of Higher-Order Cognitive Skills

    ERIC Educational Resources Information Center

    Fiorella, Logan; Vogel-Walcutt, Jennifer J.; Schatz, Sae

    2012-01-01

    Effectively presenting complex material is a crucial component of instructional design within simulation-based training (SBT) environments. One approach to facilitate the acquisition of higher-order knowledge is to embed instructional strategies within the systems themselves. Currently, however, there are few established guidelines to inform…

  10. Unprecedented Times in the Professionalisation and State Regulation of Counselling and Psychotherapy: The Role of the Higher Education Institute

    ERIC Educational Resources Information Center

    Murphy, David

    2011-01-01

    This article considers a number of issues facing those involved in counselling and psychotherapy training within United Kingdom Higher Education Institutes. It is proposed that the increasing professionalisation of counselling and psychotherapy has significant implications for lecturers and trainers. The article will explore the tension between…

  11. Quality after the Cuts? Higher Education Practitioners' Accounts of Systemic Challenges to Teaching Quality in Times of "Austerity"

    ERIC Educational Resources Information Center

    Feigenbaum, Anna; Iqani, Mehita

    2015-01-01

    What are the ramifications of current changes in the higher education landscape in the UK for the ways in which teaching staff perceive their teaching practices? What impact are funding cuts, increases in student fees and the concomitant increased workloads having on faculty morale? How might this influence "quality cultures" in teaching…

  12. Universities' Autonomy in Times of Changing Higher Education Governance: A Study of the Swiss Academic Labour Market

    ERIC Educational Resources Information Center

    Baschung, Lukas; Goastellec, Gaele; Leresche, Jean-Philippe

    2011-01-01

    Although eternally debated, the issue of autonomy in higher education is rarely analysed in its complexity. To address this issue, this article uses an analytical matrix which combines the distinction between substantive and procedural autonomy and the distinction between HEI governing bodies, academic professions and individual academics. This…

  13. Just-in-Time Research: A Call to Arms for Research into Mobile Technologies in Higher Education

    ERIC Educational Resources Information Center

    Byrne-Davis, Lucie; Dexter, Hilary; Hart, Jo; Cappelli, Tim; Byrne, Ged; Sampson, Ian; Mooney, Jane; Lumsden, Colin

    2015-01-01

    Mobile technologies are becoming commonplace in society and in education. In higher education, it is crucial to understand the impact of constant access to information on the development of the knowledge and competence of the learner. This study reports on a series of four surveys completed by UK-based medical students (n = 443) who received…

  14. 2,3,7,8-Tetrachlorodibenzo-p-dioxin equivalents in tissues of birds at Green Bay, Wisconsin, USA

    USGS Publications Warehouse

    Jones, Paul D.; Giesy, John P.; Newsted, John L.; Verbrugge, David A.; Beaver, Donald L.; Ankley, Gerald T.; Tillitt, Donald E.; Lodge, Keith B.; Niemi, Gerald J.

    1993-01-01

    The environment has become contaminated with complex mixtures of planar, chlorinated hydrocarbons (PCHs) such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and structurally similar compounds. Because the potencies of individual congeners to cause the same adverse effects vary greatly and the relative as well as absolute concentrations of individual PCH vary among samples from different locations, it is difficult to assess the toxic effects of these mixtures on wildlife. These compounds can cause a number of adverse effects, however, because the toxic effects which occur at ecologically-relevant concentrations such as embryo-lethality and birth defects appear to be mediated through the same mechanism, the potency of individual congeners can be reported relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) which is the most toxic congener in the PCH class. The concentations of 2,3,7,8-TCDD Equivalents (TCDD-EQ) were determined in the tissues of aquatic and terrestrial birds of Green Bay, Wisconsin by the H4IIE bioassay system and compared toxic equivalency factors (TEFs) with the concentration predicted by the use of toxic equivalency factors applied to concentrations of PCH, which were determined by instrumental analyses. Concentrations of TCDD-EQ ranged from 0.52 to 440 ng/kg, wet weight. The greatest concentrations occurred in the fish-eating birds. Concentrations of TCDD-EQ, which were determined by the two methods were significantly correlated, but the additive model which used the TEFs with concentrations of measured PCB, PCDD and PCDF congeners underestimated the concentrations of TCDD-EQ measured by the H4IIE bioassay by an average of 57%. This is thought to be due to contributions from un-quantified PCH, which are known to occur in the environment. Of the quantified PCH congeners, PCDD and PCDF contributed a small portion of the TCDD-EQ in the aquatic birds, while most of the

  15. Residence and Migration of First-Time Freshmen Enrolled in Higher Education Institutions: Fall 1994. E.D. TABS.

    ERIC Educational Resources Information Center

    Barbett, Samuel

    This report presents 23 tables of data on residence and migration of first-time freshmen based on the 1994 "Fall Enrollment" survey, part of the Integrated Postsecondary Education Data System. The survey counted 2.14 million first-time freshmen. More than 366,000 (17 percent) migrated between states. The percent of freshmen who left…

  16. Examining the Potential Impact of Full Tuition Fees on Mature Part-Time Students in English Higher Education

    ERIC Educational Resources Information Center

    Shaw, Angela

    2014-01-01

    This paper examines current part-time mature learners' views on the potential impact upon future students as full fees are introduced from 2012. It investigates the problems which part-time mature learners may face with the advent of student loans and subsequent debt, given that they are usually combining complex lives with their studies, with…

  17. Different tumours induced by benzo(a)pyrene and its 7,8-dihydrodiol injected into adult mouse salivary gland.

    PubMed Central

    Wigley, C. B.; Amos, J.; Brookes, P.

    1978-01-01

    A comparison has been made between the carcinogenic activities of benzo(a)pyrene and the proposed proximate carcinogen, benzo(a)pyrene 7,8-dihydrodiol, in the adult C57BL mouse submandibular salivary gland. In preliminary studies using a range of doses, the dihydrodiol was slightly less active than the parent hydrocarbon in this system. There was a difference in the type of tumour induced by the 2 compounds. Benzo(a)pyrene induced tumours of the salivary glands at the site of injection, whereas the dihydrodiol induced malignant lymphosarcomas, particularly of the thymus, which were often metastatic to other orgnas. Possible reasons for the different sites of action of the 2 compounds are discussed. PMID:580763

  18. Footprints of past earthquakes revealed in the afterslip of the 2010 Mw 7.8 Mentawai tsunami earthquake

    NASA Astrophysics Data System (ADS)

    Feng, Lujia; Barbot, Sylvain; Hill, Emma M.; Hermawan, Iwan; Banerjee, Paramesh; Natawidjaja, Danny H.

    2016-09-01

    The 2010 Mw 7.8 Mentawai tsunami earthquake marks one of the first tsunami earthquakes to have postseismic deformation observed by geodetic instruments. The Sumatran GPS Array has recorded the postseismic deformation following this event continuously for >5 years. The spatiotemporal evolution of the postseismic deformation is well explained by velocity-strengthening frictional sliding on the Sunda megathrust. Our results show that the 2010 afterslip progressed downdip relative to the 2010 coseismic rupture. The southeastern portion of the afterslip region overlaps the area that slipped during the main shock and afterslip of the 2007 Mw 8.4 Bengkulu earthquake, while the northwestern portion slipped an area without recent large earthquakes. By incorporating pre-earthquake stress conditions into quasi-dynamic models, we demonstrate that the preceding cumulative slip from the 2007 sequence might have caused a ˜0.1 MPa difference in pre-earthquake Coulomb stress between the southeastern and northwestern portions of the afterslip region.

  19. Complex multifault rupture during the 2016 Mw 7.8 Kaikōura earthquake, New Zealand.

    PubMed

    Hamling, Ian J; Hreinsdóttir, Sigrun; Clark, Kate; Elliott, John; Liang, Cunren; Fielding, Eric; Litchfield, Nicola; Villamor, Pilar; Wallace, Laura; Wright, Tim J; D'Anastasio, Elisabetta; Bannister, Stephen; Burbidge, David; Denys, Paul; Gentle, Paula; Howarth, Jamie; Mueller, Christof; Palmer, Neville; Pearson, Chris; Power, William; Barnes, Philip; Barrell, David J A; Van Dissen, Russ; Langridge, Robert; Little, Tim; Nicol, Andrew; Pettinga, Jarg; Rowland, Julie; Stirling, Mark

    2017-03-23

    On 14th November 2016, the northeastern South Island of New Zealand was struck by a major Mw 7.8 earthquake. Field observations, in conjunction with InSAR, GPS, and seismology reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 km along both mapped and unmapped faults, before continuing offshore at its northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface, extensive uplift along much of the coastline and widespread anelastic deformation including the ~8 m uplift of a fault-bounded block. This complex earthquake defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation, and should motivate re-thinking of these issues in seismic hazard models.

  20. Rupture model of Mw 7.8 2015 Gorkha, Nepal earthquake: Constraints from GPS measurements of coseismic offsets

    NASA Astrophysics Data System (ADS)

    Yadav, Rajeev Kumar; Roy, P. N. S.; Gupta, Sandeep Kumar; Khan, P. K.; Catherine, J. K.; Prajapati, Sanjay K.; Kumar, Amit; Puviarasan, N.; Bhu, Harsh; Devachandra, M.; Malik, Javed; Kundu, Bhaskar; Debbarma, Chandrani; Gahalaut, V. K.

    2017-01-01

    We estimate coseismic offsets at 20 sites in India due to the 25 April 2015 Gorkha, Nepal (Mw 7.8) earthquake. Only four sites in the Indian region, immediately to the south of the rupture, showed discernible coseismic horizontal offsets ranging between 3 and 7 mm toward north. We invert these offsets along with 13 other offsets at GPS sites in Nepal and 33 offsets at sites in China, for the estimation of slip distribution on the causative rupture. We assume that rupture occurred on the Main Himalayan Thrust (MHT). In our estimated slip model, high slip reaching ∼5 m occurred east of the mainshock epicenter, and the slip on rupture terminated close to the Main Boundary Thrust (MBT). Thus the rupture for this earthquake remained blind, increasing the potential for future earthquake in the shallow, updip unruptured part of the MHT.

  1. Maintaining Quality in Troubled Times. Pacific Rim Association for Higher Education Annual Conference (2nd, Seattle, Washington, October 13-14, 1981).

    ERIC Educational Resources Information Center

    Pacific Rim Association for Higher Education.

    Proceedings of the Pacific Rim Association for Higher Education 1981 conference are summarized. Authors and the summarized papers are as follows: "Maintaining Quality in Troubled Times: The University Perspective" (George M. Beckmann); "Maintaining Quality in Troubled Times: The Community College Perspective" (Don A. Morgan);…

  2. The Hidden Benefits of Part-Time Higher Education Study to Working Practices: Is There a Case for Making Them More Visible?

    ERIC Educational Resources Information Center

    Callender, Claire; Little, Brenda

    2015-01-01

    Within the UK, part-time study is now seen as important in meeting wider government objectives for higher education (HE) and for sustainable economic growth through skills development. Yet, measures to capture the impact of HE may not be wholly appropriate to part-time study. In particular, the continuing focus on tangible, economic measures may…

  3. An optimization-based approach for solving a time-harmonic multiphysical wave problem with higher-order schemes

    NASA Astrophysics Data System (ADS)

    Mönkölä, Sanna

    2013-06-01

    This study considers developing numerical solution techniques for the computer simulations of time-harmonic fluid-structure interaction between acoustic and elastic waves. The focus is on the efficiency of an iterative solution method based on a controllability approach and spectral elements. We concentrate on the model, in which the acoustic waves in the fluid domain are modeled by using the velocity potential and the elastic waves in the structure domain are modeled by using displacement. Traditionally, the complex-valued time-harmonic equations are used for solving the time-harmonic problems. Instead of that, we focus on finding periodic solutions without solving the time-harmonic problems directly. The time-dependent equations can be simulated with respect to time until a time-harmonic solution is reached, but the approach suffers from poor convergence. To overcome this challenge, we follow the approach first suggested and developed for the acoustic wave equations by Bristeau, Glowinski, and Périaux. Thus, we accelerate the convergence rate by employing a controllability method. The problem is formulated as a least-squares optimization problem, which is solved with the conjugate gradient (CG) algorithm. Computation of the gradient of the functional is done directly for the discretized problem. A graph-based multigrid method is used for preconditioning the CG algorithm.

  4. Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1-4 during regeneration of the rat submandibular gland.

    PubMed

    Shimizu, Osamu; Yasumitsu, Tomohiro; Shiratsuchi, Hiroshi; Oka, Shunichi; Watanabe, Tatsuhisa; Saito, Tadahito; Yonehara, Yoshiyuki

    2015-10-01

    Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the development of the submandibular gland. Although regeneration of submandibular glands follows a similar process to their development, it is unknown how FGFs and FGFRs are distributed during regeneration of submandibular gland. The aim of this study was to determine the localization of FGFs and FGFRs during such regenerative processes. After 7 days' obstruction, the submandibular glands were collected at days 0, 1, 3, 7, 11 and 14 after duct release to study regeneration. The regenerative processes of the submandibular gland were investigated by immunohistochemistry for FGF-2, 7, 8, 10 and FGFR-1-4. Immunohistochemical staining revealed that FGF-2 was moderately expressed in the epithelial cells of duct-like structures (DLS) and newly formed acinar cells (NFAC) at days 0-7, and strongly in intercalated duct (ICD) at control gland and Day 7-14. FGF-7 was localized moderately in NFAC and DLS. FGF-8 was localized moderately in the epithelial cells of DLS during regeneration. Strong positive immunoreactions for FGF-10 were found in NFAC and the epithelial cells of DLS during regeneration, as well as the ICD and lateral surfaces of the maturing acinar cells (MAC). FGFR-1 was expressed moderately in the ICD, and weakly in the NFAC and MAC. Positive immunoreactions for FGFR-2 were not observed during regeneration. Additionally, FGFR-4 was detected strongly in the ICD and slightly in NFAC. These findings suggest that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

  5. Oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by oxyl radicals produced by photolysis of azo compounds.

    PubMed

    Shao, Jie; Geacintov, Nicholas E; Shafirovich, Vladimir

    2010-05-17

    Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG(*+)/8-oxodG(-H)* radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO*) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO*), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG(*+)/8-oxodG(-H)* radicals with superoxide (O(2)(*-)) and ROO* radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Gh(ox)) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2',3',5'-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5'-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Gh(ox) and 5'-d(CCATC[Gh(ox)]CTACC products.

  6. Tangent Adjoint Methods In a Higher-Order Space-Time Discontinuous-Galerkin Solver For Turbulent Flows

    NASA Technical Reports Server (NTRS)

    Diosady, Laslo; Murman, Scott; Blonigan, Patrick; Garai, Anirban

    2017-01-01

    Presented space-time adjoint solver for turbulent compressible flows. Confirmed failure of traditional sensitivity methods for chaotic flows. Assessed rate of exponential growth of adjoint for practical 3D turbulent simulation. Demonstrated failure of short-window sensitivity approximations.

  7. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of operation ranch hand

    SciTech Connect

    Pirkle, J.L.; Wolfe, W.H.; Patterson, D.G.; Needham, L.L.; Philips, D.L. ); Michalek, J.E.; Miner, J.C.; Peterson, M.R. )

    1989-01-01

    A half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; commonly known as dioxin) in serum has been measured in 36 Air Force Vietnam Veterans of Operation Ranch Hand, which was the operation that aerially sprayed the herbicide Agent Orange in Vietnam. From serum specimens taken in 1982 and 1987, the median half-life of 2,3,7,8-TCDD in these Ranch Hand veterans was found to be 7.1 yr (95% confidence interval about the median of 5.8-9.6 yr). These veterans reported no civilian exposure to dioxin or herbicides. Concentrations of 2,3,7,8-TCDD in the 1982 serum specimens from these veterans ranged from 16.9 to 423 parts per trillion on a lipid weight basis. The half-life estimates were not associated with the concentration of 2,3,7,8-TCDD in the 1982 serum specimens. This half-life of 7.1 yr is much longer than the half-life of 2,3,7,8-TCDD reported in animals but is consistent with recent evidence from other human exposures to 2,3,7,8-TCDD.

  8. 7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome.

    PubMed

    Tian, Mi; Zeng, Yan; Hu, Yilan; Yuan, Xiuxue; Liu, Shumin; Li, Jie; Lu, Pan; Sun, Yao; Gao, Lei; Fu, Daan; Li, Yi; Wang, Shasha; McClintock, Shawn M

    2015-02-01

    Fragile X syndrome (FXS) is characterized by immature dendritic spine architectures and cognitive impairment. 7, 8-Dihydroxyflavone (7, 8-DHF) has recently been identified as a high affinity tropomyosin receptor kinase B (TrkB) agonist. The purpose of this paper was to examine the utility of 7, 8-DHF as an effective pharmacotherapeutic agent that targets dendritic pathology and cognitive impairments in FXS mutant. We synthesized pharmacologic, behavioral, and biochemical approaches to examine the effects of 7, 8-DHF on spatial and fear memory functions, and morphological spine abnormalities in fragile X mental retardation 1 (Fmr1) gene knock-out mice. The study found that 4 weeks of treatment with 7, 8-DHF improved spatial and fear memory, and ameliorated morphological spine abnormalities including the number and elongation of spines in the hippocampus and amygdala. Further mechanism analysis revealed that 7, 8-DHF enhanced the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) GluA1 receptor, but reduced the normal levels of GluA2 at the synapses in Fmr1. Potentially related to drug-induced changes in AMPA receptor subunits, 7, 8-DHF at the synapses led to phosphorylation of specific serine sites on subunits Ser818 and Ser813 of GluA1, and Ser880 of GluA2, as well as phosphorylation of TrkB, calcium/calmodulin-dependent protein kinase II, and protein kinase C. However, 7, 8-DHF neither affected behavioral performance nor increased TrkB phosphorylation in WT mice, which suggested that it had FXS-specific correcting effect. Altogether, these results demonstrated that 7, 8-DHF improved learning and memory, and reduced abnormalities in spine morphology, thus providing a potential pharmacotherapeutic strategy for FXS.

  9. The Competence Of 7,8-Diacetoxy-4-Methylcoumarinand Other Polyphenolic Acetates In Mitigating The Oxidative Stress And Their Role In Angiogenesis.

    PubMed

    Joshi, Rini; Arora, Shvetambri; Kumar, Ajit; Manral, Sushma; Rohil, Vishwajeet; Goel, Sanjay; Priya, Nivedita; Singh, Prabhjot; Ponnan, Prija; Chatterji, Suvro; Dwarakanath, Bilikere S; Saluja, Daman; Rawat, Diwan S; Prasad, Ashok K; Saso, Luciano; Kohli, Ekta; DePass, Anthony L; Bracke, Marc E; Parmar, Virinder S; Raj, Hanumantharao G

    2014-12-09

    The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8-Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by variousacetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMC-induced angiogenesis with the involvement of VEGF was established.

  10. The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis.

    PubMed

    Joshi, Rini; Arora, Shvetambri; Kumar, Ajit; Manral, Sushma; Rohil, Vishwajeet; Goel, Sanjay; Priya, Nivedita; Singh, Prabhjot; Ponnan, Prija; Chatterji, Suvro; Dwarakanath, Bilikere S; Saluja, Daman; Rawat, Diwan S; Prasad, Ashok K; Saso, Luciano; Kohli, Ekta; DePass, Anthony L; Bracke, Marc E; Parmar, Virinder S; Raj, Hanumantharao G

    2015-01-01

    The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8- Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by various acetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMC-induced angiogenesis with the involvement of VEGF was established.

  11. Enhanced stress and changes to regional seismicity due to the 2015 Mw 7.8 Gorkha, Nepal, earthquake on the neighbouring segments of the Main Himalayan Thrust

    NASA Astrophysics Data System (ADS)

    Chan, Chung-Han; Wang, Yu; Almeida, Rafael; Yadav, R. B. S.

    2017-01-01

    In this study we evaluate stress evolution and change in seismic hazard after the 2015 Gorkha earthquake sequence. We take a methodology usually used in areas with well-established seismic monitoring and apply it to an area with a sparse dataset and a limited time observation window. Our goal is to validate this approach as a rapid response tool for seismic forecasting after large earthquakes. We propose a long-term seismic forecasting model of the Main Himalayan Thrust using the historical earthquake catalogue and regional paleo-seismicity. Through application of the rate-and-state friction model, we evaluate short-term rate evolution after the Gorkha earthquake. The long elapsed time since the last megathrust event and the mainshock coseismic stress increase on the Main Himalayan Thrust suggest high seismic potential in the Lalitpur and Lamjung areas along the fault system. We also calculate the stress change on optimally oriented planes in the region and model the regional seismicity rate using a smoothing kernel method and seismicity since 1921. The location of the consequent earthquakes coincides with areas of high background seismicity rate and areas where stress was enhanced by the Mw 7.8 mainshock and Mw 7.3 aftershock. We model the change of seismic rate over time and project a fast decrease, due to the short aftershock duration assumption we use.

  12. Flexible Pedagogies: Part-Time Learners and Learning in Higher Education. Flexible Pedagogies: Preparing for the Future Series

    ERIC Educational Resources Information Center

    McLinden, Michael

    2013-01-01

    This publication focuses on national and international policy initiatives to develop a better understanding of part-time learners and the types of flexibility that may enhance their study especially pedagogically. As part of our five-strand research project "Flexible Pedagogies: preparing for the future" it: (1) highlights the challenges…

  13. Recruitment and Retention of Full-Time Engineering Faculty, Fall 1980. Higher Education Panel Report Number 52.

    ERIC Educational Resources Information Center

    Atelsek, Frank J.; Gomberg, Irene L.

    The extent of faculty vacancies in colleges of engineering, the effects of such vacancies upon research and instructional programs, and the nature of the competition between academia and industry in hiring engineering faculty were surveyed. The focus is on permanent full-time faculty positions in the following major engineering fields:…

  14. Pulling Structured Inequality into Higher Education: The Impact of Part-Time Working on English University Students

    ERIC Educational Resources Information Center

    Humphrey, Robin

    2006-01-01

    This paper explores the social and academic effects of term-time working on undergraduate students at an English university. Data initially collected via a survey of student social relationships were enhanced by the inclusion of end-of-year academic performance. Various inferential statistical techniques were used to identify these effects. Path…

  15. Does a Higher Incidence of Break Times in Primary Schools Result in Children Being More Physically Active?

    ERIC Educational Resources Information Center

    Kobel, Susanne; Kettner, Sarah; Erkelenz, Nanette; Kesztyüs, Dorothea; Steinacker, Jürgen M.

    2015-01-01

    Background: Regular physical activity (PA) has multiple benefits to health; however, the majority of schoolchildren do not reach PA guidelines of 60 minutes of moderate to vigorous PA (MVPA) daily. During the school day, break times are often the only opportunity for children to be physically active. This study investigated PA levels during school…

  16. The Economic Domino Effect: A Phenomenological Study Exploring Community College Faculty's Lived Experiences during Financial Hard Times in Higher Education

    ERIC Educational Resources Information Center

    Taylor, Tridai A.

    2014-01-01

    This qualitative study explored the lived experiences of eight full-time community college faculty members who taught during the economic crisis of 2008. The study was guided by the central research question, "How do community college faculty members describe their lived experiences regarding the recent economic crisis of 2008 and its impact…

  17. A new approach to measure single-event related brain activity using real-time fMRI: feasibility of sensory, motor, and higher cognitive tasks.

    PubMed

    Posse, S; Binkofski, F; Schneider, F; Gembris, D; Frings, W; Habel, U; Salloum, J B; Mathiak, K; Wiese, S; Kiselev, V; Graf, T; Elghahwagi, B; Grosse-Ruyken, M L; Eickermann, T

    2001-01-01

    Real-time fMRI is a rapidly emerging methodology that enables monitoring changes in brain activity during an ongoing experiment. In this article we demonstrate the feasibility of performing single-event sensory, motor, and higher cognitive tasks in real-time on a clinical whole-body scanner. This approach requires sensitivity optimized fMRI methods: Using statistical parametric mapping we quantified the spatial extent of BOLD contrast signal changes as a function of voxel size and demonstrate that sacrificing spatial resolution and readout bandwidth improves the detection of signal changes in real time. Further increases in BOLD contrast sensitivity were obtained by using real-time multi-echo EPI. Real-time image analysis was performed using our previously described Functional Imaging in REal time (FIRE) software package, which features real-time motion compensation, sliding window correlation analysis, and automatic reference vector optimization. This new fMRI methodology was validated using single-block design paradigms of standard visual, motor, and auditory tasks. Further, we demonstrate the sensitivity of this method for online detection of higher cognitive functions during a language task using single-block design paradigms. Finally, we used single-event fMRI to characterize the variability of the hemodynamic impulse response in primary and supplementary motor cortex in consecutive trials using single movements. Real-time fMRI can improve reliability of clinical and research studies and offers new opportunities for studying higher cognitive functions.

  18. In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes.

    PubMed

    Smith, Jordan N; Mehinagic, Denis; Nag, Subhasree; Crowell, Susan R; Corley, Richard A

    2017-03-05

    Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14μM), and higher intrinsic clearance at lower substrate concentrations (<0.07μM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.

  19. Impact of 2,3,7,8-TCDD exposure on survival, growth, and behavior of osprey`s breeding in Wisconsin, USA

    SciTech Connect

    Woodford, J.E.; Karasov, W.H.; Meyer, M.W.; Chambers, L.

    1998-07-01

    Osprey (Pandion halieatus) eggs collected from areas 7 km downstream from two bleached-kraft mill facilities from 1992 to 1996 contained much higher levels of 2,3,7,8-tetrachlordibenzo-p-dioxin than eggs collected from two reference areas upstream. Levels in eggs of the remaining planar halogenated hydrocarbon congeners and other nonplanar organochlorines were not statistically different between the contaminated and upstream areas. The authors placed eggs from the contaminated area into nests at both reference areas (group A) and eggs from the reference areas into nests at the contaminated area (group B). No significant differences in egg hatching or chick fledging rates were observed between these groups and nests left unmanipulated at both reference areas (group C) and the contaminated area (group D). Mass increase rates of chicks differed significantly, with the highest rates from group C and the lowest rates from group B. This difference cannot be easily attributed to differences in parental test attentiveness or food provisioning, which were greater at the contaminated area. The authors conclude that although current planar halogenated hydrocarbon exposure levels were not affecting hatching and fledging rates, they may have affected chick growth.

  20. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on early life stage development of the fathead minnow (Pimephales promelas)

    SciTech Connect

    Winden, P.J.J. de; Donselaar, E.G. van; Herwig, H.J.

    1994-12-31

    Eggs of fathead minnow were exposed to graded concentrations (0.1--100 ppt) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 24 C for 5 days. Exposure started about one hour after fertilization. The medium was refreshed daily. At day 6 (one day posthatching), body lengths were measured. A dose-dependent retardation of growth (from 1 to 30%) was observed in the range from 0.1 to 20 ppt TCDD. At higher concentrations, growth reduction remained the same but mortality still increased. Microscopic observations of the TCDD-exposed embryos revealed a number of deviations from the normal early development. Initial changes consisted of congestion of the blood flow in the caudal tail area and in the yolk sac vascular complex, followed by hemorrhages. At a later stage, pericardial edema and generalized edema were observed. In addition the embryos revealed, anaemia, decreased amounts of dermal and retinal melanin, shortened mandibles, degeneration of heart tissue, absence of swim bladder, decreased utilization of yolk sac material and a curved chords. The results indicate that embryonic development of the fathead minnow is very sensitive to TCDD. It might prove a useful model for further embryotoxic studies.

  1. High-resolution seismic tomography of the 2015 Mw7.8 Gorkha earthquake, Nepal: Evidence for the crustal tearing of the Himalayan rift

    NASA Astrophysics Data System (ADS)

    Pei, Shunping; Liu, Hongbing; Bai, Ling; Liu, Yanbing; Sun, Quan

    2016-09-01

    The Mw7.8 Gorkha earthquake struck Nepal and ruptured the boundary between the Indian and Eurasian plates. We conducted 2-D Pg wave tomography to clarify the seismogenic structure and try to understand causal mechanisms for this large earthquake, using the aftershock data recorded by 15 broadband seismic stations located near the China-Nepal border. Our high-resolution results show that coseismic slip area of the main shock is consistent with the high P wave velocity anomaly, and the region of maximum slip has a larger area with higher velocity than the region of initial slip, possibly resulting in the dominant low-frequency radiation of energy observed after the dominant high-frequency radiation of energy in the source rupture process. The boundary between these regions of contrasting high and low seismic velocity anomalies suggests a potential crustal tearing at the southern end of the Tangra Yum Co Rift, possibly resulting from different thrust speeds in the Greater Himalaya.

  2. Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants

    PubMed Central

    Feng, Yu; Forsell, Mattias N. E.; Flynn, Barbara; Adams, William; Loré, Karin; Seder, Robert; Wyatt, Richard T.; Karlsson Hedestam, Gunilla B.

    2013-01-01

    Covalent conjugation of immune-stimulatory compounds to protein antigens is a potential means to self-adjuvant non-replicating subunit vaccines. Previously, it was demonstrated that covalent coupling of a Toll-like receptor (TLR) ligand to the exterior HIV-1 envelope glycoprotein, gp120, enhanced its immunogenicity. However, the consequences of chemical conjugation to gp120 on broadly neutralizing antibody (bNAb) epitopes were so far not examined. Here, we conjugated a TLR7/8 ligand to lysine residues on gp120 using NHS-PEO8-maleimide linkers and investigated if this affected Ab recognition of the CD4 binding site (CD4bs), a highly conserved target for bNAbs. We demonstrate that the recognition of the CD4bs was reduced following coupling, especially at a higher coupling ratio. These results have implications for the coupling of ligands to vaccine antigens where elicitation of humoral immune responses to specific neutralizing determinants is desired. PMID:24074567

  3. DFT study of the adsorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin on pristine and Ni-doped boron nitride nanotubes.

    PubMed

    Wang, Ruoxi; Zhang, Dongju; Liu, Chengbu

    2017-02-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are highly toxic to humans and the environment. Developing efficient methods to detect or remove these pollutants is particularly important and urgent. Boron nitride nanotubes (BNNTs) with low dimension and high surface-to-volume ratio might be one of promising materials for the adsorption of PCDD/Fs. Here we present a density functional theory (DFT) study on the interaction of the pristine and Ni doped (8,0) single-walled BNNTs with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener among PCDD/F family. The calculated results show that the pristine BNNT intrinsically interacts with TCDD via physisorption with π-π stacking interaction, in contrast, the Ni-doped BNNT presents much higher reactivities toward TCDD. The impurity Ni atom plays a crucial role for capturing TCDD molecule. We also find that the Ni doping introduces the local electronic states within the band gap of the BNNT and induces magnetism in the doped systems. The present results are expected to provide useful guidance for the potential application of BNNTs as adsorption materials for detecting or removing dioxin pollutants.

  4. The effect of 7,8-methylenedioxylycoctonine-type diterpenoid alkaloids on the toxicity of tall larkspur (Delphinium spp.) in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Delphinium spp. contain numerous norditerpenoid alkaloids which are structurally delineated as 7, 8-methylenedioxylycoctonine (MDL) and N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids. The toxicity of many tall larkspur species has been primarily attributed to their high concentra...

  5. 41 CFR 302-7.8 - At what location can CONUS-to-CONUS or OCONUS-to-CONUS HHG shipments be temporarily stored?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT (PBP&E) General Rules § 302-7.8 At what location can CONUS-to-CONUS or...

  6. 41 CFR 302-7.8 - At what location can CONUS-to-CONUS or OCONUS-to-CONUS HHG shipments be temporarily stored?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS, PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT, (PBP&E) AND BAGGAGE ALLOWANCE General Rules § 302-7.8 At what location can...

  7. 41 CFR 302-7.8 - At what location can CONUS-to-CONUS or OCONUS-to-CONUS HHG shipments be temporarily stored?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT (PBP&E) General Rules § 302-7.8 At what location can CONUS-to-CONUS or...

  8. 2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulates proliferation of HAPI microglia by affecting the Akt/GSK-3β/cyclin D1 signaling pathway.

    PubMed

    Xu, Guangfei; Li, Yuanye; Yoshimoto, Katsuhiko; Wu, Qiyun; Chen, Gang; Iwata, Takeo; Mizusawa, Noriko; Wan, Chunhua; Nie, Xiaoke

    2014-01-30

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that induces apoptosis of neurons and a pro-inflammatory response in microglial cells. First, we found that TCDD induced proliferation of HAPI microglial cells in a dose- and time-dependent manner. Flow cytometry analysis showed that this proliferation by TCDD was due to mainly enhancing the G1 to S phase transition. Next, it was found that TCDD treatment led to up-regulation of cyclin D1, which induces cell cycle progression from G1 to S phase, in a time-dependent manner. As for molecular mechanism, we revealed that TCDD was capable of inducing Akt phosphorylation and activation, resulting in phosphorylation and inactivation of glycogen synthase kinase-3β (GSK-3β). Inactivated GSK-3β attenuated proteasomal degradation of cyclin D1 by reducing Thr(286)-phosphorylated cyclin D1 levels. Moreover, inactivated GSK-3β increased cyclin D1 gene transcription by increasing its transcription factor β-catenin in the nucleus. Further, blockage of phosphoinositide 3-kinase/Akt kinase with their specific inhibitors, LY294002 and Akt 1/2 kinase inhibitor, significantly reduced TCDD-enhanced proliferation of HAPI microglial cells. In conclusion, TCDD stimulates proliferation of HAPI microglial cells by affecting the Akt/GSK-3β/cyclin D1 signaling pathway.

  9. The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

    SciTech Connect

    Yao, Cheng Catsby.

    1989-01-01

    Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

  10. Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver.

    PubMed

    Stinchcombe, S; Buchmann, A; Bock, K W; Schwarz, M

    1995-06-01

    The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell division and cell death (apoptosis) in glutathione S-transferase (GST-P)-positive liver foci were analyzed in diethylnitrosamine-initiated female Wistar rats that were treated with TCDD, either acutely for 3 days or chronically for 115 days. Apoptotic bodies were quantitated in liver sections simultaneously stained for GST-P expression and H&E using a novel fluorescence microscopic detection method which greatly facilitates recognition of apoptotic bodies due to their high level of eosin fluorescence. While TCDD treatment only marginally affected cell division in GST-P-positive liver foci, as estimated by 5-bromo-2'-deoxyuridine-labelling, apoptotic indices were decreased to approximately 60% and approximately 10% of control values after acute and chronic TCDD treatment, respectively. In normal liver tissue, apoptotic indices were only slightly reduced by TCDD treatment, suggesting selective inhibition of apoptosis in the enzyme-altered cell population by the dioxin. Since inhibition of apoptosis in GST-P-positive liver foci was by far more pronounced than changes in cell division, our data suggest that the promoting activity of TCDD is preferentially mediated by a decrease of apoptosis in enzyme-altered liver foci.

  11. Reactions of vitamin E and its model compound 2,2,5,7,8-pentamethylchroman-6-ol with ozone

    SciTech Connect

    Liebler, D.C.; Matsumoto, Shigenobu; Matsuo, Mitsuyoshi; Iitaka, Yoichi

    1993-01-01

    Reaction of vitamin E [(R,R,R,)-{alpha}-tocopherol] with ozone in acetonitrile yielded {alpha}-tocopheryl quinone and its precursor 8{alpha}-hydroxytocopherone, which accounted for approximately 30% of the products at <50% {alpha}-tocopherol oxidation. In addition, two novel products were identified as epimers of 10-acetyl-7-(4{prime},8{prime},12{prime}-trimethyl tridecyl)-3,4,7-trimethyl-2-oxo - 1,6-dioxaspiro[4.5]-deca-3,9-diene. These spiro products were formed in equal amounts in a combined yield of approximately 33% after complete {alpha}-tocpherol oxidation. Ozonation of the vitamin E model compound 2,2,5,7,8-pentamethylchroman-6-ol yielded an analogous spiro product, 10-acetyl-3,4,7,7-tetramethyl-2-oxo-1,6-dioxaspiro[4.5]deca-3,9-diene, whose structure was confirmed by X-ray crystallography. The spiro products may be formed by ozone addition to the chroman ring and subsequent rearrangement to ring-opened hydroxyacid products, which yield spiro products by ring closure due to dehydration. Novel spiro products formed by ozonation of vitamin E may be unique markers of ozone interaction with lipid structures that contain vitamin E. 39 refs., 3 figs., 1 tab.

  12. Quantitative Detection of 8-Oxo-7,8-dihydro-2′-deoxyguanosine Using Chemical Tagging and qPCR

    PubMed Central

    2015-01-01

    8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is a commonly formed DNA lesion that is useful as a biomarker for oxidative stress. Although methods for selective quantification of 8-oxodGuo exist, there is room for additional methods that are sensitive and utilize instrumentation that is widely available. We previously took advantage of the reported reactivity of 8-oxodGuo to develop a method for detecting the lesion by selectively covalently tagging it with a molecule equipped with a biotin label that can be used subsequently with a reporting method (XueL., and GreenbergM. M. (2007) J. Am. Chem. Soc.129, 701017497789). We now report a method that can detect as little as 14 amol of 8-oxodGuo by tagging DNA with a reagent containing a disulfide that reduces background due to nonspecific binding. The reagent also contains biotin that enables capturing target DNA on streptavidin-coated magnetic beads. The captured DNA is quantified using quantitative PCR. The method is validated by comparing the amount of 8-oxodGuo detected as a function of Fe2+/H2O2/ascorbate-dose to that reported previously using mass spectrometry. PMID:24932862

  13. 2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout

    USGS Publications Warehouse

    Carvalho, Paulo S. M.

    2004-01-01

    An understanding of mechanisms of contaminant effects across levels of biological organization is essential in ecotoxicology if we are to generate predictive models for population-level effects. We applied a suite of biochemical, histological, and behavioral end points related to visual structure and function and foraging behavior to evaluate effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on swim-up rainbow trout. We detected a dose-dependent decrease in densities of retinal ganglion cells (RGC), key retinal neurons that link the eye with the brain. These changes resulted in corresponding deficits in visual/motor function including reductions in visual acuity and in scotopic and photopic thresholds due to TCDD. The loss of RGCs suggests an increase in convergence of synapses from photoreceptors to RGCs as a cellular mechanism for the visual deficits. Dose-dependent increases in immunohistochemical detection of CYP1A protein in the vasculature of the brain and eye choroid was proportional with decreased ganglion cell densities in the retina. TCDD-induced AHR-regulated effects on these tissues might be involved in the detected decrease in ganglion cell densities. Prey capture rate decreased after TCDD exposure only at the highest treatment groups evaluated. Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness.

  14. Rapid characterization of the 2015 Mw 7.8 Gorkha, Nepal, earthquake sequence and its seismotectonic context

    USGS Publications Warehouse

    Hayes, Gavin; Briggs, Richard; Barnhart, William D.; Yeck, William; McNamara, Daniel E.; Wald, David J.; Nealy, Jennifer; Benz, Harley M.; Gold, Ryan D.; Jaiswal, Kishor S.; Marano, Kristin; Earle, Paul S.; Hearne, Mike; Smoczyk, Gregory M.; Wald, Lisa A.; Samsonov, Sergey

    2015-01-01

    Earthquake response and related information products are important for placing recent seismic events into context and particularly for understanding the impact earthquakes can have on the regional community and its infrastructure. These tools are even more useful if they are available quickly, ahead of detailed information from the areas affected by such earthquakes. Here we provide an overview of the response activities and related information products generated and provided by the U.S. Geological Survey National Earthquake Information Center in association with the 2015 M 7.8 Gorkha, Nepal, earthquake. This group monitors global earthquakes 24  hrs/day and 7  days/week to provide rapid information on the location and size of recent events and to characterize the source properties, tectonic setting, and potential fatalities and economic losses associated with significant earthquakes. We present the timeline over which these products became available, discuss what they tell us about the seismotectonics of the Gorkha earthquake and its aftershocks, and examine how their information is used today, and might be used in the future, to help mitigate the impact of such natural disasters.

  15. The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal Newborn Neuron Death After Traumatic Brain Injury.

    PubMed

    Chen, Liang; Gao, Xiang; Zhao, Shu; Hu, Weipeng; Chen, Jinhui

    2015-06-01

    Previous studies in rodents have shown that after a moderate traumatic brain injury (TBI) with a controlled cortical impact (CCI) device, the adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus. There is no effective approach for preventing immature neuron death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born immature neurons. We determined that the small molecule imitating BDNF, 7, 8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons both in vitro and in vivo. Pretreatment with DHF protected immature neurons from excitotoxicity-mediated death in vitro, and systemic administration of DHF before moderate CCI injury reduced the death of adult-born immature neurons in the hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These data indicate that DHF may be a promising chemical compound that promotes immature neuron survival after TBI through activation of the BDNF signaling pathway.

  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Prevents Cardiac Valve Formation in Developing Zebrafish

    PubMed Central

    Mehta, Vatsal; Peterson, Richard E.; Heideman, Warren

    2008-01-01

    Cardiovascular malformations are one of the most common congenital birth defects observed in humans. Defects in cardiac valves disrupt normal blood flow. Zebrafish are an outstanding experimental model for studying the effects that environmental contaminants have on developmental processes. Previous research has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes blood regurgitation in the heart and reduces peripheral blood flow in embryonic zebrafish, suggesting some form of valve failure. To test this we used video microscopy to examine valve function and structure in developing zebrafish exposed to TCDD. TCDD exposure produced blood regurgitation at both the atrioventricular (AV) and bulboventricular (BV) junctions. In marked contrast to control embryos exposed to the vehicle dimethyl sulfoxide, embryos exposed to TCDD failed to form valve leaflets as the heart matured. In addition, whereas TCDD did not block initial formation of the bulbus arteriosus, we found that TCDD exposure prevented the normal growth and development of this portion of the outflow tract. TCDD altered the localization of endothelial cells at the AV and BV junctions and altered the localized expression of mRNAs bmp4 and notch1b normally associated with the nascent valves. Taken together, our results demonstrate that although TCDD does not prevent the initial specification of the presumptive valve locations, TCDD exposure produces severe alterations in valve development, leading to blood regurgitation and failing circulation in the developing zebrafish. PMID:18477685

  17. Perinatal 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Sensitizes Offspring to Angiotensin II-induced Hypertension

    PubMed Central

    Aragon, Andrea C.; Goens, M. Beth; Carbett, Eleanor; Walker, Mary K.

    2013-01-01

    In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 µg/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/d) or pressor (0.7 mg/kg/d) dose of Ang II at 3.5 mo and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickness during diastole and systole. While Ang II stimulated an increase in wall thickness, the degree of increase was equivalent between control and TCDD offspring. In contrast, perinatal TCDD exposure did not alter basal blood pressure. However, Ang II increased systolic blood pressure more rapidly and to a greater degree in TCDD offspring. Further, Ang II stimulated renal myofibroblast differentiation and collagen deposition to a greater degree, and tended to increase procollagen I mRNA in TCDD offspring, compared to controls. These data suggest that perinatal TCDD exposure increases the susceptibility of offspring to renal fibrosis and hypertension in adulthood. PMID:18670907

  18. Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

    PubMed Central

    Venkateswaran, Kavya; Shrivastava, Anju; Agrawala, Paban K.; Prasad, Ashok; Kalra, Namita; Pandey, Parvat R.; Manda, Kailash; Raj, Hanumantharao G.; Parmar, Virinder S.; Dwarakanath, Bilikere S.

    2016-01-01

    Protection of the hematopoietic system from radiation damage, and/or mitigation of hematopoietic injury are the two major strategies for developing medical countermeasure agents (MCM) to combat radiation-induced lethality. In the present study, we investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow (BM) cellularity was restored through enhanced proliferation of the stem cells. It stimulated multi-lineage expansion and differentiation of myeloid progenitors in the BM and induced proliferation of splenic progenitors thereby, facilitating hematopoietic re-population. DAMTC reduced the radiation-induced apoptotic and mitotic death in the hematopoietic compartment. Recruitment of pro-inflammatory M1 macrophages in spleen contributed to the immune-protection linked to the mitigation of hematopoietic injury. Recovery of the hematopoietic compartment correlated well with mitigation of mortality at a lethal dose of 9 Gy, leading to 80% animal survival. Present study establishes the potential of DAMTC to mitigate radiation-induced injury to the hematopoietic system by stimulating the re-population of stem cells from multiple lineages. PMID:27849061

  19. Enhanced suppressor cell activity as a mechanism of immunosuppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Clark, D.A.; Gauldie, J.; Szewczuk, M.R.; Sweeney, G.

    1981-11-01

    TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic halogenated aromatic hydrocarbon, acts in the body as a cumulative poison. The chronic immunotoxic effects of TCDD were studied in C57B1/6 male mice. Total doses of 100 ..mu..g/kg or greater produced cellular depletion in thymus, spleen, and lymph nodes, and the animals appeared sick. No cellular depletion was seen following 0.4 ..mu..g/kg, and only thymus was affected by 4 and 40 ..mu..g/kg. The antibody response to SRBC and TNP-Brucella abortus was impaired following ..mu..g/kg and the generation of alloantigen-specific cytotoxic T cells (CTL) was sensitive to as little as 0.004 ..mu..g/kg TCDD. In vitro analysis of the mechanism of suppression using limiting dilution techniques showed that TCDD did not deplete the precursors of CTL but generated cells capable of suppressing CTL generation in vitro.

  20. Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice.

    PubMed

    Venkateswaran, Kavya; Shrivastava, Anju; Agrawala, Paban K; Prasad, Ashok; Kalra, Namita; Pandey, Parvat R; Manda, Kailash; Raj, Hanumantharao G; Parmar, Virinder S; Dwarakanath, Bilikere S

    2016-11-16

    Protection of the hematopoietic system from radiation damage, and/or mitigation of hematopoietic injury are the two major strategies for developing medical countermeasure agents (MCM) to combat radiation-induced lethality. In the present study, we investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow (BM) cellularity was restored through enhanced proliferation of the stem cells. It stimulated multi-lineage expansion and differentiation of myeloid progenitors in the BM and induced proliferation of splenic progenitors thereby, facilitating hematopoietic re-population. DAMTC reduced the radiation-induced apoptotic and mitotic death in the hematopoietic compartment. Recruitment of pro-inflammatory M1 macrophages in spleen contributed to the immune-protection linked to the mitigation of hematopoietic injury. Recovery of the hematopoietic compartment correlated well with mitigation of mortality at a lethal dose of 9 Gy, leading to 80% animal survival. Present study establishes the potential of DAMTC to mitigate radiation-induced injury to the hematopoietic system by stimulating the re-population of stem cells from multiple lineages.

  1. Transcriptional profiling of TLR-4/7/8-stimulated guinea pig splenocytes and whole blood by bDNA assay

    PubMed Central

    Ching, Lance K.; Mompoint, Farah; Guderian, Jeffrey A.; Picone, Alex; Orme, Ian M.; Coler, Rhea N.; Reed, Steven G.; Baldwin, Susan L.

    2011-01-01

    Toll-like receptor (TLR) agonists are currently being examined as adjuvants for vaccines, with several lead candidates now in licensed products or in late-stage clinical development. Guinea pigs are widely used for preclinical testing of drugs and vaccines; however, evaluation of TLR agonists in this model is hindered by the limited availability of immunological tools and reagents. In this study, we validated the use of a branched-chain DNA (bDNA) assay known as the QuantiGene Plex 2.0 Reagent System for measuring innate cytokine and chemokine mRNA levels following TLR stimulation of guinea pig cells. Gene expression for T-helper-1 (Th1) polarizing cytokines (TNF-α, IL-1β, IL-12) and chemokines (CXCL1, CCL2) was upregulated following ex vivo stimulation of guinea pig splenocytes and whole blood with TLR-4 or TLR-7/8 agonists. These data confirm the utility of the QuantiGene system both as an alternative to RT-PCR for measuring transcript levels and as a high-throughput screening tool for dissecting the immunological response to TLR stimulation in guinea pigs. Overall, the QuantiGene platform is reliable, reproducible, and sensitive. These agonists have the potential to be used as adjuvant components in vaccines against various pathogens. PMID:21839740

  2. Endocrine and metabolic aspects of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    SciTech Connect

    Gorski, J.R.

    1988-01-01

    Toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were characterized in male Sprague-Dawley rats in order to elucidate the mechanism of acute toxicity of this potent halogenated hydrocarbon. Studies in TCDD-treated, pair-fed control and ad libitum-fed control rates, as well as in thyroidectomized, adrenalectomized and hypophysectomized, revealed differential hormonal, toxicologic and histophathologic responses suggesting that these manifestations of TCDD exposure are the results of an insult to intermediary metabolism. Tissue specific alterations in de novo fatty acid synthesis were directly related to differential changes observed in thyroid hormone homeostasis. The increased hepatic de novo fatty acid synthesis provided a likely mechanism for the documented fact that TCDD-treated rats lose more body weight than corresponding pair-fed controls because de novo fatty acid synthesis represents an energy inefficient metabolic process. Experiments in adrenalectomized and hypophysectomized rats led to the hypothesis that severe hypoglycemia due to inhibition of gluconeogenesis is the cause of TCDD-induced death. A subsequent characterization of gluconeogenesis in TCDD-treated rats confirmed this hypothesis.

  3. Trends in 2,3,7,8-TCDD concentrations in fish tissues downstream of pulp mills bleaching with chlorine

    SciTech Connect

    Abbott, J.D.; Hinton, S.W.

    1996-07-01

    Field measurements of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in fish tissues from riverine environments impacted by treated pulp and paper industry effluent in the US were analyzed. Data from 39 sites in 14 states across the four major US paper-making regions were assembled and analyzed to determine the annual change in lipid-normalized concentrations of TCDD in fish tissue. The results provide strong evidence of a nationwide trend of decreasing lipid-normalized TCDD concentrations in fish tissue, with 84% of the examined sites showing a decrease. While the paucity of data currently limits any conclusions regarding the statistical significance at individual sites, the overall median rate calculated indicates a 0.36 annual fractional decrease in lipid-normalized concentrations of TCDD in fish tissue (0.18 to 0.51, 95% confidence interval); the average annual fractional decrease was 0.35 (0.23 to 0.47, 95% confidence interval). Subdividing fish into benthic and nonbenthic categories resulted in rates which were not significantly different from one another for both the median and mean statistics.

  4. Effect of 5,6,7,8-tetrahydroneopterin on the bovine endothelial cell injury induced by cumene hydroperoxide.

    PubMed

    Kurobane, T; Kojima, S; Yoshimura, M; Icho, T; Kajiwara, Y; Kubota, K

    1995-07-01

    Neopterin is an 2-amino-4-hydroxypteridine derivative and a precursor of biopterin, which is derived from guanosine triphosphate. Previously, we have reported that 5,6,7,8-tetrahydroneopterin (NPH4), a reduced form of neopterin, possesses an antioxidant activity in various systems. In this study, we investigated the activity in more detailed manner and discussed the possible applications of this antioxidant. Analysis by electron spin resonance spectrometry indicated that NPH4 scavenged superoxide anion radicals and hydroxyl radicals as well. Moreover, NPH4 protected the rat brain homogenate from autoxidation. Next, we examined the effect of NPH4 on the cell injury induced by cumene hydroperoxide (CHP) in cultured bovine artery endothelial cells. The activity of lactate dehydrogenase, a marker enzyme of cell injury, was elevated by CHP in a dose-dependent manner, and this elevation was dose-dependently suppressed by NPH4. The elevation of lipid peroxide content was also inhibited by NPH4 in the same fashion. These data suggest that NPH4 would be effective against various diseases whose pathogenesis is active oxygen-related.

  5. Ground motions from the 2015 Mw 7.8 Gorkha, Nepal, earthquake constrained by a detailed assessment of macroseismic data

    USGS Publications Warehouse

    Martin, Stacey; Hough, Susan E.; Hung, Charleen

    2015-01-01

    To augment limited instrumental recordings of the Mw 7.8 Gorkha, Nepal, earthquake on 25 April 2015 (Nepali calendar: 12 Baisakh 2072, Bikram Samvat), we collected 3831 detailed media and first-person accounts of macroseismic effects that include sufficiently detailed information to assign intensities. The resulting intensity map reveals the distribution of shaking within and outside of Nepal, with the key result that shaking intensities throughout the near-field region only exceeded intensity 8 on the 1998 European Macroseismic Scale (EMS-98) in rare instances. Within the Kathmandu Valley, intensities were generally 6–7 EMS. This surprising (and fortunate) result can be explained by the nature of the mainshock ground motions, which were dominated by energy at periods significantly longer than the resonant periods of vernacular structures throughout the Kathmandu Valley. Outside of the Kathmandu Valley, intensities were also generally lower than 8 EMS, but the earthquake took a heavy toll on a number of remote villages, where many especially vulnerable masonry houses collapsed catastrophically in 7–8 EMS shaking. We further reconsider intensities from the 1833 earthquake sequence and conclude that it occurred on the same fault segment as the Gorkha earthquake.

  6. Internal Gravity Wave Induced by the Queen Charlotte Event (27 October 2012, Mw 7.8): Airglow Observation and Modeling.

    NASA Astrophysics Data System (ADS)

    Occhipinti, G.; Bablet, A.; Makela, J. J.

    2015-12-01

    The detection of the tsunami related internal gravity waves (IGWtsuna) by airglow camera has been recently validated by observation (Makela et al., 2011) and modeling (Occhipinti et al., 2011) in the case of the Tohoku event (11 March 2011, Mw 9.0). The airglow is measuring the photon emission at 630 nm, indirectly linked to the plasma density of O2+ (Link & Cogger, 1988) and it is commonly used to detect transient event in the ionosphere (Kelley et al., 2002, Makela et al., 2009, Miller et al., 2009). The modeling of the IGWtsuna clearly reproduced the pattern of the airglow measurement observed over Hawaii and the comparison between the observation and the modeling allows to recognize the wave form and allow to explain the IGWtsuna arriving before the tsunami wavefront at the sea level (Occhipinti et al., 2011). Approaching the Hawaiian archipelagos the tsunami propagation is slowed down (reduction of the sea depth), instead, the IGWtsuna, propagating in the atmosphere/ionosphere, conserves its speed. In this work, we present the modeling of the new airglow observation following the Queen Charlotte event (27 October 2012, Mw 7.8) that has been recently detected, proving that the technique can be generalized for smaller events. Additionally, the effect of the wind on the IGWtsuna, already evocated in the past, is included in the modeling to better reproduce the airglow observations. All ref. here @ www.ipgp.fr/~ninto

  7. Phytotoxicity effects and biological responses of Arabidopsis thaliana to 2,3,7,8-tetrachlorinated dibenzo-p-dioxin exposure.

    PubMed

    Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad

    2014-06-01

    Dioxins are persistent organic pollutants. Their bioaccumulation in the food chain makes dioxins a considerable risk for human health. The use of plants for removing toxic organic compounds, including dioxins, is a safe and efficient strategy. Herein we studied the toxicity effects and the biological responses in Arabidopsis thaliana to 2',3',7',8'-tetrachlorinated dibenzo-p-dioxin (TCDD) exposure. First, TCDD-induced toxicity was demonstrated using several parameters including, a decrease in seed germination, a loss in fresh weight with a striking decrease in chlorophyll content, but not in carotenoids, and an augmentation in the biomass of the lateral roots system, but not in the elongation of the primary root. Uptake of TCDD by Arabidopsis was confirmed. Responses to TCDD-exposure were marked by an enhanced level of hydrogen peroxide H2O2 production and a massive stimulation of anti-oxidative enzyme activities. Moreover, a significant variation in the transcript level of transcription factor genes, bHLH, MYB and AP2-EREBP was detected in Arabidopsis shoot and an up-regulation of WRKY, MYB and IAA was observed in the root. Our results illustrate the TCDD-induced toxicity effects and the biological responses of Arabidopsis to TCDD. Better understanding of the plants ability to detoxifydioxins would help to improve their use as a safe bioremediators.

  8. 2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure prevents cardiac valve formation in developing zebrafish.

    PubMed

    Mehta, Vatsal; Peterson, Richard E; Heideman, Warren

    2008-08-01

    Cardiovascular malformations are one of the most common congenital birth defects observed in humans. Defects in cardiac valves disrupt normal blood flow. Zebrafish are an outstanding experimental model for studying the effects that environmental contaminants have on developmental processes. Previous research has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes blood regurgitation in the heart and reduces peripheral blood flow in embryonic zebrafish, suggesting some form of valve failure. To test this we used video microscopy to examine valve function and structure in developing zebrafish exposed to TCDD. TCDD exposure produced blood regurgitation at both the atrioventricular (AV) and bulboventricular (BV) junctions. In marked contrast to control embryos exposed to the vehicle dimethyl sulfoxide, embryos exposed to TCDD failed to form valve leaflets as the heart matured. In addition, whereas TCDD did not block initial formation of the bulbus arteriosus, we found that TCDD exposure prevented the normal growth and development of this portion of the outflow tract. TCDD altered the localization of endothelial cells at the AV and BV junctions and altered the localized expression of mRNAs bmp4 and notch1b normally associated with the nascent valves. Taken together, our results demonstrate that although TCDD does not prevent the initial specification of the presumptive valve locations, TCDD exposure produces severe alterations in valve development, leading to blood regurgitation and failing circulation in the developing zebrafish.

  9. Perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to angiotensin II-induced hypertension.

    PubMed

    Aragon, Andrea C; Goens, M Beth; Carbett, Eleanor; Walker, Mary K

    2008-01-01

    In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 microg/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/day) or pressor (0.7 mg/kg/day) dose of Ang II at 3.5 months and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickness during diastole and systole. While Ang II stimulated an increase in wall thickness, the degree of increase was equivalent between control and TCDD offspring. In contrast, perinatal TCDD exposure did not alter basal blood pressure. However, Ang II increased systolic blood pressure more rapidly and to a greater degree in TCDD offspring. Further, Ang II stimulated renal myofibroblast differentiation and collagen deposition to a greater degree, and tended to increase procollagen I mRNA in TCDD offspring, compared to controls. These data suggest that perinatal TCDD exposure increases the susceptibility of offspring to renal fibrosis and hypertension in adulthood.

  10. Slip model of the 2015 Mw 7.8 Gorkha (Nepal) earthquake from inversions of ALOS-2 and GPS data

    NASA Astrophysics Data System (ADS)

    Wang, Kang; Fialko, Yuri

    2015-09-01

    We use surface deformation measurements including Interferometric Synthetic Aperture Radar data acquired by the ALOS-2 mission of the Japanese Aerospace Exploration Agency and Global Positioning System (GPS) data to invert for the fault geometry and coseismic slip distribution of the 2015 Mw 7.8 Gorkha earthquake in Nepal. Assuming that the ruptured fault connects to the surface trace of the Main Frontal Thrust (MFT) fault between 84.34°E and 86.19°E, the best fitting model suggests a dip angle of 7°. The moment calculated from the slip model is 6.08 × 1020 Nm, corresponding to the moment magnitude of 7.79. The rupture of the 2015 Gorkha earthquake was dominated by thrust motion that was primarily concentrated in a 150 km long zone 50 to 100 km northward from the surface trace of the Main Frontal Thrust (MFT), with maximum slip of ˜ 5.8 m at a depth of ˜8 km. Data thus indicate that the 2015 Gorkha earthquake ruptured a deep part of the seismogenic zone, in contrast to the 1934 Bihar-Nepal earthquake, which had ruptured a shallow part of the adjacent fault segment to the east.

  11. Slip Model of the 2015 Mw 7.8 Gorkha (Nepal) Earthquake from Inversions of ALOS-2 and GPS Data

    NASA Astrophysics Data System (ADS)

    Wang, K.; Fialko, Y. A.

    2015-12-01

    We use surface deformation measurements including Interferometric Synthetic Aperture Radar (InSAR) data acquired by the ALOS-2 mission of the Japanese Aerospace Exploration Agency (JAXA) and Global Positioning System (GPS) data to invert for the fault geometry and coseismic slip distribution of the 2015 Mw 7.8 Gorkha earthquake in Nepal. Assuming that the ruptured fault connects to the surface trace of the of Main Frontal Thrust fault (MFT) between 84.34E and 86.19E, the best-fitting model suggests a dip angle of 7 degrees. The moment calculated from the slip model is 6.17*1020 Nm, corresponding to the moment magnitude of 7.79. The rupture of the 2015 Gorkha earthquake was dominated by thrust motion that was primarily concentrated in a 150-km long zone 50 to 100 km northward from the surface trace of the Main Frontal Thrust (MFT), with maximum slip of ~6 m at a depth of ~ 8 km. Data thus indicate that the 2015 Gorkha earthquake ruptured a deep part of the seismogenic zone, in contrast to the 1934 Bihar-Nepal earthquake, which had ruptured a shallow part of the adjacent fault segment to the East.

  12. IL-27 Is Essential for Suppression of Experimental Allergic Asthma by the TLR7/8 Agonist R848 (Resiquimod)

    PubMed Central

    Jirmo, Adan Chari; Daluege, Kathleen; Happle, Christine; Albrecht, Melanie; Dittrich, Anna-Maria; Busse, Mandy; Habener, Anika; Skuljec, Jelena

    2016-01-01

    Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell–driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production. Whereas R848 significantly reduced IL-5, IL-13, and IL-17, it induced IFN-γ and IL-27. Neutralization of IL-27 completely reversed the therapeutic effect of R848 in the experimental asthma model, demonstrating dependence of R848-mediated suppression on IL-27. In vitro, R848 induced production of IL-27 by murine alveolar macrophages and dendritic cells and enhanced expression of programmed death–ligand 1, whose expression on monocytes and dendritic cells has been shown to regulate peripheral tolerance in both murine and human studies. Moreover, in vitro IL-27 enhanced secretion of IFN-γ whereas it inhibited IL-5 and IL-13, demonstrating its direct effect on attenuating Th2 responses. Taken together, our study proves that R848-mediated suppression of experimental asthma is dependent on IL-27. These data provide evidence of a central role of IL-27 for the control of Th2-mediated allergic diseases. PMID:27799314

  13. 7,7,8,8-Tetracyanoquinodimethane based molecular dopants for p-type doping of OLEDs: A theoretical investigation

    SciTech Connect

    Cosimbescu, Lelia; Padmaperuma, Asanga B.; Gaspar, Daniel J.

    2011-11-15

    The array of organic conductivity dopants used for organic light emitting devices (OLED) to reduce the operating voltage and improve power efficiency is extremely limited. Here we report a comparative theoretical study between newly proposed analogs and the standard state-of-the-art conductivity dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). We used density functional theory to determine the bond lengths, bond angles and electronic properties, such as the energy of the highest occupied molecular orbital (E{sub HOMO}) and lowest occupied molecular orbital (E{sub LUMO}) states, as well as the triplet energies of the novel structures (ET). The ground state structures of the proposed molecules were optimized at the B3LYP/6-31G* level. The results show that substitution of one or two fluorine groups in the F4-TCNQ core with a substituted phenyl ring or other electron withdrawing moieties, will not substantially affect the geometry of the molecule or its electronic ability to accept electrons. The most significant finding was that the phenyl substitutions onto the TCNQ core are nearly perpendicular to the TCNQ plane, and thus there is no electronic communication between the two rings. This is extremely important, as such extension of the {pi} conjugated system would negatively affect the E{sub LUMO} and thus the electron affinity of the molecule.

  14. Transistor Properties of 2,7-Dialkyl-Substituted Phenanthro[2,1-b:7,8-b′]dithiophene

    PubMed Central

    Kubozono, Yoshihiro; Hyodo, Keita; Hamao, Shino; Shimo, Yuma; Mori, Hiroki; Nishihara, Yasushi

    2016-01-01

    A new phenacene-type molecule with five fused aromatic rings was synthesized: 2,7-didodecylphenanthro[2,1-b:7,8-b′]dithiophene ((C12H25)2-i-PDT), with two terminal thiophene rings. Field-effect transistors (FETs) using thin films of this molecule were fabricated using various gate dielectrics, showing p-channel normally-off FET properties with field-effect mobilities (μ) greater than 1 cm2 V−1 s−1. The highest μ value in the thin-film FETs fabricated in this study was 5.4 cm2 V−1 s−1, when a 150 nm-thick ZrO2 gate dielectric was used. This implies that (C12H25)2-i-PDT is very suitable for use in a transistor. Its good FET performance is fully discussed, based on electronic/topological properties and theoretical calculations. PMID:27922104

  15. 7, 8, 3'-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons.

    PubMed

    Shi, Haohong; Luo, Xingjing

    2016-07-02

    BACKGROUND 7, 8, 3'-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro. MATERIAL AND METHODS Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively. RESULTS THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine-induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons. CONCLUSIONS THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation.

  16. Detailed strip map of the Kokoxili earthquake rupture (Mw 7.8, 14/11/01) from space

    NASA Astrophysics Data System (ADS)

    Klinger, Y.; van der Woerd, J.; Tapponnier, P.; Xu, X. W.; King, G.; Chen, W. B.; Ma, W. T.; Peltzer, G.; Bowman, D.

    2003-04-01

    On 14/11/2001 a strike-slip earthquake, with Mw 7.8, occurred along the western Kunlun fault (Tibet). The earthquake produced a surface rupture about 400km long, in a very remote area. Using evidence gathered in the field, we mapped swaths of the rupture with new high-resolution, Ikonos satellite images, producing a continuous strip map of the central segment of the rupture. This map has meter-scale resolution and shows all significant strands, scarps, and cracks produced by the earthquake, as well as jogs, bends, pull-aparts, push-ups down to that scale. Over long sections, the rupture is divided in two traces. The southern trace is almost purely strike-slip while the second, located a few hundred meters to 2 km northwards, along the base of the range-front, accommodates predominant normal motion. Such slip-partitioning is less clear where the fault rupture has a more southerly azimuth. The mapping shows that the strike-slip rupture is very linear with few small, mostly transpressive transfer zones and one large pull-apart. The strike-slip offsets are typically 5 meters, but reach up to 10 meters in a few places. Normal fault scarps along the range-front have throws from 0.5 to 1 meter. High-resolution satellite images thus appear to be a powerful tool to map earthquake surface breaks. A complete map of the 400 km-long Kokoxili earthquake rupture is in progress.

  17. The Role of 7,8-Dihydroxyflavone in Preventing Dendrite Degeneration in Cortex After Moderate Traumatic Brain Injury.

    PubMed

    Zhao, Shu; Gao, Xiang; Dong, Weiren; Chen, Jinhui

    2016-04-01

    Our previous research showed that traumatic brain injury (TBI) induced by controlled cortical impact (CCI) not only causes massive cell death, but also results in extensive dendrite degeneration in those spared neurons in the cortex. Cell death and dendrite degeneration in the cortex may contribute to persistent cognitive, sensory, and motor dysfunction. There is still no approach available to prevent cells from death and dendrites from degeneration following TBI. When we treated the animals with a small molecule, 7,8-dihydroxyflavone (DHF) that mimics the function of brain-derived neurotrophic factor (BDNF) through provoking TrkB activation reduced dendrite swellings in the cortex. DHF treatment also prevented dendritic spine loss after TBI. Functional analysis showed that DHF improved rotarod performance on the third day after surgery. These results suggest that although DHF treatment did not significantly reduced neuron death, it prevented dendrites from degenerating and protected dendritic spines against TBI insult. Consequently, DHF can partially improve the behavior outcomes after TBI.

  18. Infrared, Raman and NMR spectra, conformational stability and vibrational assignment of 7,8-Dihydroxy-4-Methylcoumarin.

    PubMed

    Erdogdu, Yusuf; Saglam, Semran

    2014-11-11

    We report a combined some (infrared, Raman and NMR) spectroscopic and quantum chemistry study on 7,8-Dihydroxy-4-Methylcoumarin molecule (78D4MC). The Raman and IR spectra of 78D4MC molecule were recorded and analyzed in the region 3500-50 cm(-1) and 4000-400 cm(-1), respectively. Potential energy scans were performed at the MMFF level of theory. All possible conformers, which are results at the MMFF level theory, were re-computed at the B3LYP functional with cc-pVDZ basis set. The optimized geometrical parameters, harmonic vibrational wavenumbers and NMR chemical shifts of the most stable conformer were calculated at the B3LYP/6-311G(d,p), cc-pVTZ and cc-pVQZ level in the proximity of the isolated molecule. DFT calculations were combined with Pulay's scaled quantum mechanics force field (SQMFF) methodology in order to fit the theoretical wavenumbers to the experimental ones.

  19. Fine mapping and single nucleotide polymorphism effects estimation on pig chromosomes 1, 4, 7, 8, 17 and X

    PubMed Central

    Hidalgo, André M.; Lopes, Paulo S.; Paixão, Débora M.; Silva, Fabyano F.; Bastiaansen, John W.M.; Paiva, Samuel R.; Faria, Danielle A.; Guimarães, Simone E.F.

    2013-01-01

    Fine mapping of quantitative trait loci (QTL) from previous linkage studies was performed on pig chromosomes 1, 4, 7, 8, 17, and X which were known to harbor QTL. Traits were divided into: growth performance, carcass, internal organs, cut yields, and meat quality. Fifty families were used of a F2 population produced by crossing local Brazilian Piau boars with commercial sows. The linkage map consisted of 237 SNP and 37 microsatellite markers covering 866 centimorgans. QTL were identified by regression interval mapping using GridQTL. Individual marker effects were estimated by Bayesian LASSO regression using R. In total, 32 QTL affecting the evaluated traits were detected along the chromosomes studied. Seven of the QTL were known from previous studies using our F2 population, and 25 novel QTL resulted from the increased marker coverage. Six of the seven QTL that were significant at the 5% genome-wide level had SNPs within their confidence interval whose effects were among the 5% largest effects. The combined use of microsatellites along with SNP markers increased the saturation of the genome map and led to smaller confidence intervals of the QTL. The results showed that the tested models yield similar improvements in QTL mapping accuracy. PMID:24385854

  20. Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels in US Army Vietnam-era veterans

    SciTech Connect

    Not Available

    1988-09-02

    This study investigates whether military records can be used to identify US Army Vietnam veterans who were likely to be exposed to the herbicide Agent Orange. Serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a toxic contaminant in Agent Orange, were obtained for 646 ground combat troops who served in heavily sprayed areas of Vietnam and for 97 veterans who did not serve in Vietnam. The distributions of current TCDD levels in Vietnam and non-Vietnam veterans were nearly identical (mean in each group, approx. = 4 parts per trillion (ppt)). Only two men (both Vietnam veterans) had clearly elevated levels (> 20 ppt). Levels of TCDD did not tend to increase with greater likelihood of exposure to Agent Orange, as estimated from either military records of self-reported exposure. This study is consistent with other studies and suggests that most US Army ground troops who served in Vietnam were not heavily exposed to TCDD, except perhaps men whose jobs involved handling herbicides.

  1. Late time acceleration of the 3-space in a higher dimensional steady state universe in dilaton gravity

    SciTech Connect

    Akarsu, Özgür; Dereli, Tekin E-mail: tdereli@ku.edu.tr

    2013-02-01

    We present cosmological solutions for (1+3+n)-dimensional steady state universe in dilaton gravity with an arbitrary dilaton coupling constant w and exponential dilaton self-interaction potentials in the string frame. We focus particularly on the class in which the 3-space expands with a time varying deceleration parameter. We discuss the number of the internal dimensions and the value of the dilaton coupling constant to determine the cases that are consistent with the observed universe and the primordial nucleosynthesis. The 3-space starts with a decelerated expansion rate and evolves into accelerated expansion phase subject to the values of w and n, but ends with a Big Rip in all cases. We discuss the cosmological evolution in further detail for the cases w = 1 and w = ½ that permit exact solutions. We also comment on how the universe would be conceived by an observer in four dimensions who is unaware of the internal dimensions and thinks that the conventional general relativity is valid at cosmological scales.

  2. Building on Strengths in a Time of Retrenchment: Developing an M.Ed. in Higher Education--Student Affairs Emphasis to Train Christian Practitioners

    ERIC Educational Resources Information Center

    Morris, Jason; Haseltine, Jeffrey; Williams, Carol

    2007-01-01

    To gain approval of a new master's degree in difficult financial times, the authors applied strategies that are applicable at other institutions. Using existing internal resources to build on the university's mission was key in developing a new M.Ed. in Higher Education--Student Affairs Emphasis at Abilene Christian University. Creativity and…

  3. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin induces premature senescence of astrocytes via WNT/β-catenin signaling and ROS production.

    PubMed

    Nie, Xiaoke; Liang, Lingwei; Xi, Hanqing; Jiang, Shengyang; Jiang, Junkang; Tang, Cuiying; Liu, Xipeng; Liu, Suyi; Wan, Chunhua; Zhao, Jianya; Yang, Jianbin

    2015-07-01

    2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that could exert significant neurotoxicity in the human nervous system. Nevertheless, the molecular mechanism underlying TCDD-mediated neurotoxicity has not been clarified clearly. Herein, we investigated the potential role of TCDD in facilitating premature senescence in astrocytes and the underlying molecular mechanisms. Using the senescence-associated β-galactosidase (SA-β-Gal) assay, we demonstrated that TCDD exposure triggered significant premature senescence of astrocyte cells, which was accompanied by a marked activation of the Wingless and int (WNT)/β-catenin signaling pathway. In addition, TCDD altered the expression of senescence marker proteins, such as p16, p21 and GFAP, which together have been reported to be upregulated in aging astrocytes, in both dose- and time-dependent manners. Further, TCDD led to cell-cycle arrest, F-actin reorganization and the accumulation of cellular reactive oxygen species (ROS). Moreover, the ROS scavenger N-acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular oxidative damage and astrocyte senescence. Notably, the application of XAV939, an inhibitor of WNT/β-catenin signaling pathway, ameliorated the effect of TCDD on cellular β-catenin level, ROS production, cellular oxidative damage and premature senescence in astrocytes. In summary, our findings indicated that TCDD might induce astrocyte senescence via WNT/β-catenin and ROS-dependent mechanisms.

  4. Evaluation of the peripheral nervous system among workers employed in the production of chemicals contaminated with 2,3,7. 8-tetra-chlorodibenzo-p-dioxin. Final report

    SciTech Connect

    Sweeney, M.H.; Fingerhut, M.A.; Connally, L.B.; Hornung, R.

    1990-07-01

    The long term effects on the peripheral nervous system in workers with past exposure to production products contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) were evaluated. The severity of the current neurologic status was compared to the levels of TCDD measured in the serum of study subjects. Workers who were employed at two chemical factories at which chemicals contaminated with TCDD were manufactured, and a group of unexposed referents were assessed in a cross sectional medical study in 1987 through 1988. Questionnaires were used to collect follow-up data. There were 281 workers and 260 referents who were interviewed and medically examined. Peripheral neuropathy was found in about 18% of workers and 19% of referents. Serum TCDD levels ranged from 2 to 3390 parts per trillion (ppt) for 272 workers and from 2 to 20ppt for 86 referents tested. No dose-response relationship was observed between TCDD levels present at the time of the examination and the occurrence of peripheral neuropathy in the previously exposed population. The authors conclude that exposure to TCDD caused no excess chronic peripheral neuropathy in a group of exposed workers compared to unexposed referents.

  5. Changes in fibrinopeptide A peptides in the sera of rats chronically exposed to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    PubMed

    Chen, Xi; Ma, Shi-wei; Ma, Xiao-ming; Xu, Yuan-jing; Tang, Nai-jun

    2012-03-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine disruptors. To investigate peptide changes in the sera of rats chronically exposed to TCDD and to explore the association of these changes with liver morphology, TCDD was administrated to male rats at doses of 140, 350, and 875 ng/kg/week for 29 weeks. Serum was collected and proteomic analysis was performed using automated Bruker Daltonics ClinProt with matrix-assisted laser desorption/ionization time-of-flight mass spectrometer. One peptide at 1740.89 was found to be significantly decreased and further identified with nano LC-MS/MS system. The MS BLAST homology search engine reported the peptide to be a partial sequence of fibrinopeptide A. Liver fatty degeneration and necrosis were assessed by hematoxylin and eosin staining. Liver fatty degeneration and necrosis were both found to be significantly increased after TCDD exposure. Levels of fibrinopeptide A were significantly correlated with liver fatty degeneration and necrosis.

  6. Effect of tocopherol on biochemical blood parameters in pleuritis-induced rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Całkosiński, Ireneusz; Rosińczuk-Tonderys, Joanna; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Bazan, Justyna; Dobrzyński, Maciej; Majda, Jacek; Gamian, Andrzej

    2015-06-01

    The aim of this study was to evaluate the effect of tocopherol on pleuritis-induced rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were treated with a single TCDD dose of 5 μg/kg body weight (b.w.) and then for 3 weeks they were daily supplemented with tocopherol at a dose of 30 mg/kg b.w. The inflammation was initiated by intrapleural injection of a single dose of 1% carrageenin solution in a volume of 0.15 ml. Changes in biochemical blood parameters were measured three times at the 24th, 72nd and 120th hour of pleuritis and the blood was collected from 20 animals of each group of rats (group with the control inflammation; group treated with TCDD and with control inflammation; group treated with TCDD, supplemented with tocopherol and with the inflammation). The following biochemical parameters were measured: tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-4, IL-6, procollagen, telopeptide, fibrinogen, cholesterol, urea, creatinine, aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT). Daily supplementation of tocopherol caused significant changes in the level of TNF, IL-1, IL-4, IL-6, urea, creatinine, AspAT and AlAT. According to the results of these studies, we suggest that tocopherol supplementation in high doses could act as a protective treatment to improve liver metabolism.

  7. The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hematological parameters during experimentally induced pleuritis in rats.

    PubMed

    Całkosiński, Ireneusz; Rosińczuk-Tonderys, Joanna; Bazan, Justyna; Dzierzba, Katarzyna; Całkosińska, Monika; Majda, Jacek; Dobrzyński, Maciej; Bronowicka-Szydełko, Agnieszka

    2013-04-01

    Proper functioning of homeostatic mechanisms is characteristic for every healthy organism and enables adapting to environmental changes. These complicated systematic reactions can neutralize the harmful stress factors leading to various inflammatory reactions. The aim of this study was to determine dynamic changes in the inflammatory reaction after single 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration of 5 μg/kg body weight into rats with experimentally induced pleuritis. These changes were observed by monitoring the hematological blood parameters during inflammation. The obtained results proved that dioxins contribute to various changes in the character of the inflammatory response. TCDD administration before pleuritis initiation caused an increase of lymphocytes and significant decrease of the number of neutrophils during inflammation. The current study proved that administration of low TCDD dose (seven times lower than used in other studies) can cause thymus, spleen, or lymphatic gland atrophy. This finding indicates the toxic influence of small TCDD dose especially on the immune system.

  8. 2,3,7,8 tetrachlorodibenzodioxin in fish from the Pigeon river of Eastern Tennessee: Its toxicity and mutagenicity as revealed by the Ames Salmonella Assay

    SciTech Connect

    Blevins, R.D. )

    1990-04-01

    Levels of 2,3,7,8 tetrachlorodibenzodioxin (TCDD)were determined in both striated muscle (fillets) and whole body extracts of fish specimens harvested during a two year period (1987-1989) from the Pigeon River (between Hartford and Newport) of Eastern Tennessee. Whole body (wet weight) fish extract levels as high as 117 {mu}g/kg body weight and composite fish fillet (wet weight) extract levels as high 87 {mu}g/kg fillet weight were observed. Pure TCDD was found to be highly toxic to the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA1535 at TCDD dosages which exceeded 825 ng/ml in the top agar of the Ames Salmonella assay. An 825 ng/ml TCDD dosage was not mutagenic to any of the tested Salmonella strains, (both with and without metabolic activation (S9) mix). However, when both acidic and alcohol fish extracts from the Pigeon River were tested for mutagenicity, several of the fish extracts were found to be mutagenic to Salmonella strains TA97, TA98, and TA100 (having mutagenic ratios which greatly exceeded the 2.5 {times} spontaneous ratio). These mutagenic extracts also demonstrated mutagenic dose-response curves. Other chemicals within the extracts as well as synergistic effects may account for the mutagenicity.

  9. Comparison of serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin with indirect estimates of Agent Orange exposure among Vietnam veterans. Final report

    SciTech Connect

    Not Available

    1989-09-01

    The report tests the validity of several indirect methods for estimating the exposure of ground troops to Agent Orange in Vietnam during 1966-69. The study identified a sample of U.S. Army Vietnam veterans of that era and asked them to have blood drawn so that the level of 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) in serum could be measured. These veterans were selected from among those who served in 65 combat battalions in III Corps, a heavily sprayed part of Vietnam around Saigon. The men selected had all served only one tour in Vietnam and had been discharged with a pay grade of E1-E5, after having spent, on the average, over 300 days in Vietnam. The sample was chosen after the veterans had been stratified on likelihood of exposure (time and space proximity to recorded sprays) according to military records. For comparison, a sample of non-Vietnam U.S. Army veterans of the same era was also examined. The results show no meaningful association between TCDD levels and indirect estimate of Agent Orange exposure in Vietnam, with or without adjustment for other characteristics of the veterans, including age, race, body mass index, and self-reported civilian occupational and home herbicide exposure.

  10. Using a time-domain higher-order boundary element method to simulate wave and current diffraction from a 3-D body

    NASA Astrophysics Data System (ADS)

    Liu, Zhen; Teng, Bin; Ning, De-Zhi; Sun, Liang

    2010-06-01

    To study wave-current actions on 3-D bodies a time-domain numerical model was established using a higher-order boundary element method (HOBEM). By assuming small flow velocities, the velocity potential could be expressed for linear and higher order components by perturbation expansion. A 4th-order Runge-Kutta method was applied for time marching. An artificial damping layer was adopted at the outer zone of the free surface mesh to dissipate scattering waves. Validation of the numerical method was carried out on run-up, wave exciting forces, and mean drift forces for wave-currents acting on a bottom-mounted vertical cylinder. The results were in close agreement with the results of a frequency-domain method and a published time-domain method. The model was then applied to compute wave-current forces and run-up on a Seastar mini tension-leg platform.

  11. Identification of major Streptococcus suis serotypes 2, 7, 8 and 9 isolated from pigs and humans in upper northeastern Thailand.

    PubMed

    Nutravong, Thitima; Angkititrakul, Sunpetch; Jiwakanon, Netchanok; Wongchanthong, Wanlaya; Dejsirilerts, Surang; Nawa, Yukifumi

    2014-09-01

    Streptococcus suis serotype 2 infections occur in many provinces of north-eastern Thailand, knowledge concerning the prevalence of the common S. suis serotypes (1, 1/2, 2, 5, 7, 8, 9, 14 and 16) among healthy and diseased pigs in upper northeastern Thailand remains limited. This study investigated S. suis isolates from pigs (healthy and diseased) and also from humans using 11 conventional biochemical tests, 16S rDNA PCR and sequence analysis and multiplex PCR genotyping of porcine cps and gdh. Thirty-three isolates were obtained between 2009 and 2012 from blood or cerebrospinal fluid of patients from northeastern Thailand previously diagnosed with S. suis infection, based on clinical symptoms and laboratory diagnosis using 11 biochemical tests and PCR detection of 16S rDNA and cps. Eleven S. suis isolates were obtained between 2006 and 2009 from diseased pigs with clinical signs and laboratory diagnoses. In addition, 43 isolates obtained from 741 nasal swab cultures of slaughtered pigs between 2011 and 2012 were included. All three methods showed similar sensitivity in detection of S. suis from clinical and diseased pig specimens, although in healthy pigs, the 11 conventional biochemical methods yielded 2.3% false positives, and the gdh PCR detection method exhibited 31% false negatives. S. suis was present among healthy pigs in 8 of 10 provinces in upper northeastern Thailand, giving an average prevalence of 5.7% (range 1%-17%) using conventional methods together with 16S rDNA PCR assay. False positives by conventional methods were due to species with similar phenotypes, such as viridian streptococci, and are not statistically different from those obtained with the 16S rDNA PCR method, and the false negatives using gdh PCR assay will require further investigation. As S. suis was recovered from both diseased and healthy pigs, raw or undercooked pork products should be considered unsafe for handling or consumption in these regions of Thailand.

  12. Combined TLR7/8 and TLR9 Ligands Potentiate the Activity of a Schistosoma japonicum DNA Vaccine

    PubMed Central

    Wang, Xuefeng; Dong, Liyang; Ni, Hongchang; Zhou, Sha; Xu, Zhipeng; Hoellwarth, Jason Shih; Chen, Xiaojun; Zhang, Rongbo; Chen, Qiaoyun; Liu, Feng; Wang, Jun; Su, Chuan

    2013-01-01

    Background Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). Methodology/Principal Findings In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4+CD25+Foxp3+ regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens. Conclusions Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion. PMID:23593527

  13. Spectral Expansion Inversion for the 2015 Mw 7.8 Gorkha Earthquake: Investigation on the Boundaries of Rupture

    NASA Astrophysics Data System (ADS)

    Xu, X.; Sandwell, D. T.

    2015-12-01

    The current standard approach for static or quasi-static slip inversion with geodetic data is by discretizing a fault into a number of patches whose size is mostly smaller than their depth, thus a straightforward inversion usually leads to wild oscillations in slip. This is because forward elastic models that relate slip at depth to surface deformation contain an exponential upward continuation term [Steketee 1958], which makes this problem inherently non-unique [Parker 1994]. To stabilize the inversion, a smoothness regularization is usually applied along with a non-negative slip constraint (e.g. left lateral slip only) [Jonsson et al 2002]. Sometimes a checkerboard test is performed in order to understand the resolving power of the data [Tong et al 2010]. While this approach can provide us with one reasonable model, we would also like to establish the complete set of models that is equally consistent with the data and assumptions. Here we investigate the possibility of applying linear inverse theory [Parker 1977] to slip inversion, in particular, the spectral expansion approach. This approach inverts for slip as a linear combination of orthonormal functions that span the model space. More important the spectral expansion approach isolates the parts of the model that are well determined by the data from those that are not. Based on the upward continuation nature of this problem, it is almost certain the part with lowest order or largest wavelength (i.e. seismic moment) is well determined. We plan to apply this approach to the recent Mw 7.8 Gorkha earthquake with ScanSAR acquisitions from ALOS-2 [Lindsey et al 2015] to investigate the distribution of the slip. The results will be reported at the meeting.

  14. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation.

    PubMed

    Harvey, Wendy A; Jurgensen, Kimberly; Pu, Xinzhu; Lamb, Cheri L; Cornell, Kenneth A; Clark, Reilly J; Klocke, Carolyn; Mitchell, Kristen A

    2016-02-17

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are non-parenchymal cells that store vitamin A when quiescent. Upon liver injury, activated HSCs lose this storage ability and instead function in the development and maintenance of inflammation and fibrosis through the production of pro-inflammatory mediators and collagen type I. Reports that TCDD exposure disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC activity. The human HSC line LX-2 was used to test the hypothesis that TCDD treatment directly activates HSCs. Results indicate that exposure to 10nM TCDD almost completely inhibited lipid droplet storage in LX-2 cells cultured with retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, expression of α-smooth muscle actin, and production of monocyte chemoattractant protein-1 (MCP-1), all of which are characteristics of activated HSCs. However, TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with the potent profibrogenic mediator, transforming growth factor-β. The TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was abolished when phosphoinositide 3-kinase was inhibited. These results indicate that HSCs are susceptible to direct modulation by TCDD and that TCDD likely increases HSC activation through a multi-faceted mechanism.

  15. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation

    PubMed Central

    Harvey, Wendy A.; Jurgensen, Kimberly; Pu, Xinzhu; Lamb, Cheri L.; Cornell, Kenneth A.; Clark, Reilly J.; Klocke, Carolyn; Mitchell, Kristen A.

    2016-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are non-parenchymal cells that store vitamin A when quiescent. Upon liver injury, activated HSCs lose this storage ability and instead function in the development and maintenance of inflammation and fibrosis through the production of pro-inflammatory mediators and collagen type I. Reports that TCDD exposure disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC activity. The human HSC line LX-2 was used to test the hypothesis that TCDD treatment directly activates HSCs. Results indicate that exposure to 10 nM TCDD almost completely inhibited lipid droplet storage in LX-2 cells cultured with retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, expression of α-smooth muscle actin, and production of monocyte chemoattractant protein-1 (MCP-1), all of which are characteristics of activated HSCs. However, TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with the potent profibrogenic mediator, transforming growth factor-β. The TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was abolished when phosphoinositide 3-kinase was inhibited. These results indicate that HSCs are susceptible to direct modulation by TCDD and that TCDD likely increases HSC activation through a multifaceted mechanism. PMID:26860701

  16. Embryotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the ring-necked pheasant

    SciTech Connect

    Nosek, J.A.; Craven, S.R. . Dept. of Wildlife Ecology); Sullivan, J.R. . Wisconsin Dept. of Natural Resources); Gendron-Fitzpatrick, A. . Research Animal Veterinarian and Research Animal Resource Committee); Peterson, R.E. . School of Pharmacy and Environmental Toxicology Center)

    1993-07-01

    Fertilized eggs of ring-necked pheasants (Phasianus colchicus) were injected into the albumin or yolk with vehicle or graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on day 0 of embryonic development and toxicity was assessed in 1-d-old hatchlings and 28-d-old chicks. The most sensitive effect of in ovo TCDD exposure was induction of hepatic ethoxyresorufin-O-deethylase (EROD) activity in 1-d-old hatchlings. The ED50 for this response was 312 pg TCDD/g egg. Embryo mortality was the most sensitive sign of toxicity. The TCDD dose that caused 50% mortality above control (LD50) when injected into the egg albumin or yolk was 1,354 and 2,182 pg TCDD/g egg, respectively. At egg TCDD doses up to and including 1,000 pg TCDD/g egg, no effect was detected in 1-d-old hatchlings and 28-d-old chicks in body growth, organ weights, carcass morphometrices, incidence of edema, or incidence of histological alterations in the liver, spleen, heart, Bursa of Fabricius, or thymus. Egg TCDD doses as high as 1,000 pg TCDD/g egg also had no effect on cardiac morphometrices or incidence of cardiac malformations in 1-d-old hatchlings, or on antibody-mediated immunity in 28-d-old chicks. The authors conclude that embryo mortality is the most sensitive sign of TCDD toxicity in the ring-necked pheasant following in ovo exposure.

  17. Differential neutrophil activation in viral infections: Enhanced TLR‐7/8‐mediated CXCL8 release in asthma

    PubMed Central

    Van Ly, David; Spann, Kirsten; Reading, Patrick C.; Burgess, Janette K.; Hartl, Dominik; Baines, Katherine J.; Oliver, Brian G.

    2015-01-01

    Abstract Background and objective Respiratory viral infections are a major cause of asthma exacerbations. Neutrophils accumulate in the airways and the mechanisms that link neutrophilic inflammation, viral infections and exacerbations are unclear. This study aims to investigate anti‐viral responses in neutrophils from patients with and without asthma and to investigate if neutrophils can be directly activated by respiratory viruses. Methods Neutrophils from peripheral blood from asthmatic and non‐asthmatic individuals were isolated and stimulated with lipopolysaccharide (LPS) (1 μg/mL), f‐met‐leu‐phe (fMLP) (100 nM), imiquimod (3 μg/mL), R848 (1.5 μg/mL), poly I:C (10 μg/mL), RV16 (multiplicity of infection (MOI)1), respiratory syncytial virus (RSV) (MOI1) or influenza virus (MOI1). Cell‐free supernatants were collected after 1 h of neutrophil elastase (NE) and matrix metalloproteinase (MMP)‐9 release, or after 24 h for CXCL8 release. Results LPS, fMLP, imiquimod and R848 stimulated the release of CXCL8, NE and MMP‐9 whereas poly I:C selectively induced CXCL8 release only. R848‐induced CXCL8 release was enhanced in neutrophils from asthmatics compared with non‐asthmatic cells (P < 0.01). RSV triggered the release of CXCL8 and NE from neutrophils, whereas RV16 or influenza had no effect. Conclusion Neutrophils release CXCL8, NE and MMP‐9 in response to viral surrogates with R848‐induced CXCL8 release being specifically enhanced in asthmatic neutrophils. Toll‐like receptor (TLR7/8) dysregulation may play a role in neutrophilic inflammation in viral‐induced exacerbations. PMID:26477783

  18. An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design.

    PubMed

    Fustinoni, S; Campo, L; Manini, P; Buratti, M; Waidyanatha, S; De Palma, G; Mutti, A; Foa, V; Colombi, A; Rappaport, S M

    2008-09-01

    The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg m(-3) and 133 microg m(-3) for reinforced plastics workers, 3.4 mg m(-3) and 12 microg m(-3) for varnish workers, and <0.3 mg m(-3) and <5 microg m(-3) for controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid, phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as cysteinyl adducts of serum albumin (but not those of haemoglobin) were significantly associated with exposure status (controls

  19. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    SciTech Connect

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  20. Guanine and 7,8-dihydro-8-oxo-guanine-specific oxidation in DNA by chromium(V).

    PubMed

    Sugden, Kent D; Martin, Brooke D

    2002-10-01

    The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate the lesions generated from this oxidation process. Reaction of Cr(V)-Salen with synthetic oligonucleotides produced guanine-specific lesions that were not 8-oxo-2'-deoxyguanosine, based on the inability of iridium(IV) to further oxidize these sites. Oxidation products were identified using a 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-G) containing oligonucleotide to increase the yields of product for identification by electrospray ionization mass spectrometry. The guanine-based lesions observed by mass spectrometry corresponded to the lesions guanidinohydantoin and spiroiminodihydantoin. The effects of these Cr(V)-Salen-induced lesions on DNA replication fidelity was assayed using a polymerase-based misincorporation assay. These lesions produced G --> T transversion mutations and polymerase stops at levels greater than those observed for 8-oxo-G. These data suggest a model by which chromate can cause DNA damage leading to mutations and cancer.

  1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces premature activation of the KLF2 regulon during thymocyte development.

    PubMed

    McMillan, Brian J; McMillan, Susanne N; Glover, Ed; Bradfield, Christopher A

    2007-04-27

    The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) causes numerous and diverse toxic events via activation of the aryl hydrocarbon receptor, including atrophy of the thymus. Exposure to TCDD induces acute thymocyte cell loss, which occurs concomitantly with proliferation arrest and premature emigration of triple negative (TN; CD4(-), CD8(-), CD3(-)) T cell progenitors. In this report, we demonstrate that TCDD exposure results in dysregulation of KLF2 (Kruppel-like factor 2) expression in developing thymocytes. The Klf2 gene encodes an Sp1-like zinc finger transcription factor that functions as a central regulator of T lymphocyte proliferation and trafficking. During normal thymocyte development, KLF2 is expressed exclusively in CD4 and CD8 single positive T cells and promotes a nonproliferative, promigratory phenotype. In mice exposed to TCDD, however, the Klf2 gene is prematurely expressed in TN thymocytes. Administration of a 100 microg/kg dose of TCDD results in a approximately 15-fold induction of KLF2 as early as the TN2 (CD44(+), CD25(+)) stage of development and immediately precedes acute cell loss in the TN3, TN4, and double positive (CD4(+), CD8(+)) cell stages. Induction of KLF2 occurs within 12 h of TCDD exposure and is fully dependent on expression of the aryl hydrocarbon receptor. In addition, TCDD exposure alters the expression of several factors comprising the KLF2 regulon, including Edg1/S1P(1), beta(7) integrin, CD52, Cdkn2d (cyclin-dependent kinase inhibitor 2D), s100a4, and IL10R alpha. These findings indicate that the pollutant TCDD interferes with early thymopoeisis via ectopic expression of the KLF2 regulon.

  2. On the coseismic ionospheric disturbances after the Nepal Mw7.8 earthquake on April 25, 2015 using GNSS observations

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Yao, Yibin; Yao, Wanqiang

    2017-01-01

    Nepal Mw7.8 earthquake occurred at 06:11:26 UTC on April 25, 2015. The epicenter was located at 28.147°N, 84.708°E, with the focal depth of 15 km. In this paper, the coseismic ionospheric disturbances were analyzed using Vertical Total Electron Content from Global Navigation Satellite System (GNSS) observations obtained from 309 continuous tracking stations around the epicenter. The results show that significant ionospheric disturbances occurred within 10 min after the earthquake. The maximum anomaly reached 1.34 TECU; the maximum duration was 10 min; the farthest anomaly was found beyond 3000 km from the epicenter. The ionospheric response was attributed to two modes: shock acoustic waves and Rayleigh wave. Within 500 km from the epicenter, ionosphere anomaly was induced by both waves, with average propagating speed of 0.61 and 1.62 km/s, respectively. With increasing epicentral distance, the ionospheric disturbances caused by acoustic waves gradually weakened, whereas Rayleigh waves induced ionosphere disturbances reached up to 3000 km from the epicenter. The propagation speed of Rayleigh waves gradually increased to 2.74 km/s while the distance from the epicenter to sub-ionospheric point was over 1500 km. The occurrence of the disturbances appeared strong directivity. The amplitudes of the disturbances were large to the south of the epicenter. In contrast, to the northwest of the epicenter, few disturbances were observed, and the amplitudes of these disturbances were small. In general, the amplitude of the anomaly decreased with increasing epicentral distance. However, the amplitude of the anomaly increased at 1500-2500 km to the northeast of the epicenter.

  3. 2,3,7,8-Tetracholorodibenzo-p-dioxin exposure disrupts granule neuron precursor maturation in the developing mouse cerebellum.

    PubMed

    Collins, Loretta L; Williamson, Mary A; Thompson, Bryan D; Dever, Daniel P; Gasiewicz, Thomas A; Opanashuk, Lisa A

    2008-05-01

    The widespread environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been linked to developmental neurotoxicity associated with abnormal cerebellar maturation in both humans and rodents. TCDD mediates toxicity via binding to the aryl hydrocarbon receptor (AhR), a transcription factor that regulates the expression of xenobiotic metabolizing enzymes and growth regulatory molecules. Our previous studies demonstrated that cerebellar granule neuron precursor cells (GNPs) express transcriptionally active AhR during critical developmental periods. TCDD exposure also impaired GNP proliferation and survival in vitro. Therefore, this study tested the hypothesis that TCDD exposure disrupts cerebellar development by interfering with GNP differentiation. In vivo experiments indicated that TCDD exposure on postnatal day (PND) 6 resulted in increased expression of a mitotic marker and increased thickness of the external granule layer (EGL) on PND10. Expression of the early differentiation marker TAG-1 was also more pronounced in postmitotic, premigratory granule neurons of the EGL, and increased apoptosis of GNPs was observed. On PND21, expression of the late GNP differentiation marker GABA(A alpha 6) receptor (GABAR(A alpha 6)) and total estimated cell numbers were both reduced following exposure on PND6. Studies in unexposed adult AhR(-/-) mice revealed lower GABAR(A alpha 6) levels and DNA content. In vitro studies showed elevated expression of the early differentiation marker p27/Kip1 and the GABAR(A alpha 6) in GNPs following TCDD exposure, and the expression patterns of proteins related to granule cell neurite outgrowth, beta III-tubulin and polysialic acid neural cell adhesion molecule, were consistent with enhanced neuroblast differentiation. Together, our data suggest that TCDD disrupts a normal physiological role of AhR, resulting in compromised GNP maturation and neuroblast survival, which impacts final cell number in the cerebellum.

  4. Detecting Hidden Aftershocks of the 2015 Mw 7.8 Gorkha Earthquake Using Multiple Global Seismic Arrays

    NASA Astrophysics Data System (ADS)

    Ghosh, A.; LI, B.

    2015-12-01

    Spatio-temporal evolution of aftershocks is important for the study of rupture extent [McCann et al., 1979], stress transfer [King et al., 1994], postseismic deformation [Hsu et al., 2006; Sladen et al., 2010], hazard assessment and forecasting of future seismicity [e.g., Cocco et al., 2010]. However, many aftershocks remain undetected by the global network due to the limitation of the density and distribution of seismic instruments. In this study, we use the back-projection method with multiple global seismic arrays to detect the hidden earthquakes (not recorded by current standard global earthquake catalog) following the 2015 Mw 7.8 Gorkha earthquake. There are 140 aftershocks in the global catalog within 10 days since the mainshock. Using array methods, we are able to detect about twice as many events near the mainshock. According to the Advanced National Seismic System (ANSS) comprehensive earthquake catalog, the first aftershock happened 4 minutes after the mainshock. We detect aftershocks even before that event. This shows that back-projection can be used to detect early aftershocks in global scale, which usually remain undetected by the arrival of various seismic phases immediately following a large earthquake [Lengline et al., 2012]. Detection of these hidden aftershocks provides a more complete picture of the spatiotemporal distribution of aftershock activity and helps improve the completeness of the global standard aftershock catalog. Our improved aftershock catalog shows east-west aftershocks distribution (Figure 1), similar to the ANSS catalog. In addition, we detect significant number of aftershocks north, south, and within the coseismic rupture area. The improved aftershock catalog using existing global seismic arrays enables us to better study aftershocks dynamics, stress evolution and earthquake characteristics.

  5. Kinetics, structure, and mechanism of 8-Oxo-7,8-dihydro-2'-deoxyguanosine bypass by human DNA polymerase η.

    PubMed

    Patra, Amritraj; Nagy, Leslie D; Zhang, Qianqian; Su, Yan; Müller, Livia; Guengerich, F Peter; Egli, Martin

    2014-06-13

    DNA damage incurred by a multitude of endogenous and exogenous factors constitutes an inevitable challenge for the replication machinery. Cells rely on various mechanisms to either remove lesions or bypass them in a more or less error-prone fashion. The latter pathway involves the Y-family polymerases that catalyze trans-lesion synthesis across sites of damaged DNA. 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxoG) is a major lesion that is a consequence of oxidative stress and is associated with cancer, aging, hepatitis, and infertility. We have used steady-state and transient-state kinetics in conjunction with mass spectrometry to analyze in vitro bypass of 8-oxoG by human DNA polymerase η (hpol η). Unlike the high fidelity polymerases that show preferential insertion of A opposite 8-oxoG, hpol η is capable of bypassing 8-oxoG in a mostly error-free fashion, thus preventing GC→AT transversion mutations. Crystal structures of ternary hpol η-DNA complexes and incoming dCTP, dATP, or dGTP opposite 8-oxoG reveal that an arginine from the finger domain assumes a key role in avoiding formation of the nascent 8-oxoG:A pair. That hpol η discriminates against dATP exclusively at the insertion stage is confirmed by structures of ternary complexes that allow visualization of the extension step. These structures with G:dCTP following either 8-oxoG:C or 8-oxoG:A pairs exhibit virtually identical active site conformations. Our combined data provide a detailed understanding of hpol η bypass of the most common oxidative DNA lesion.

  6. Inhibition of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin depends on protein biosynthesis.

    PubMed

    Chopra, Martin; Gährs, Maike; Haben, Melina; Michels, Christine; Schrenk, Dieter

    2010-08-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant. Most of the toxic effects of TCDD are believed to be mediated by high-affinity binding to the aryl hydrocarbon receptor (AhR) and subsequent effects on gene transcription and protein expression. TCDD causes cancer in multiple tissues in different animal species and is classified as a class 1 human carcinogen. In initiation-promotion studies, TCDD was shown to be a potent liver-tumor promotor. Among other theories it has been hypothesized that TCDD promotes tumor growth by preventing initiated cells from correctly executing apoptosis. In this study, we examined the effects of TCDD on apoptosis induced by UV-C light, ochratoxin A (OTA), and cycloheximide (CHX) in primary rat hepatocytes. Both UV-C light and OTA caused caspase activation and nuclear apoptotic effects. CHX did not activate caspases but nevertheless caused DNA fragmentation and chromatin condensation. TCDD inhibited UV-C light-induced apoptosis and this effect seemed to be dependent on AhR-activation as was shown by employing an AhR antagonist. In contrast to UV-C light-induced apoptosis, TCDD failed to protect primary rat hepatocytes from OTA- or CHX-induced apoptosis. Since both of these compounds inhibit protein biosynthesis as was demonstrated by measuring the incorporation of radiolabeled leucin and protein expression of cytochrome P450 1A1, we propose that the inhibition of apoptosis by TCDD depends on protein biosynthesis. Either TCDD induces some anti-apoptotic protein in an AhR-dependent manner or inhibits pro-apoptotic proteins induced by UV irradiation.

  7. 7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice.

    PubMed

    Feng, Pingfu; Akladious, Afaf A; Hu, Yufen; Raslan, Yousef; Feng, James; Smith, Phillip J

    2015-10-01

    Brain-derived neurotrophic factor (BDNF) binds to Tropomyosin-receptor-kinase B (TrkB) receptors that regulate synaptic strength and plasticity in the mammalian nervous system. 7,8-Dihydroxyflavone (DHF) is a recently identified small molecule Trk B agonist that has been reported to ameliorate depression, attenuate the fear response, improve memory consolidation, and exert neuroprotective effects. Poor and disturbed sleep remains a symptom of major depressive disorder and most current antidepressants affect sleep. Therefore, we conducted sleep/wake recordings and concomitant measurement of brain orexins, endogenous peptides that suppress sleep, in mice for this study. Baseline polysomnograph recording was performed for 24 h followed by treatment with either 5 mg/kg of DHF or vehicle at the beginning of the dark phase. Animals were sacrificed the following day, one hour after the final treatment with DHF. Orexin A and B were quantified using ELISA and radioimmunoassay, respectively. Total sleep was significantly decreased in the DHF group, 4 h after drug administration in the dark phase, when compared with vehicle-treated animals. This difference was due to a significant decrease of non-rapid eye movement sleep, but not rapid eye movement sleep. DHF increased power of alpha and sigma bands but suppressed power of gamma band during sleep in dark phase. Interestingly, hypothalamic levels of orexin A were also significantly decreased in the DHF group (97 pg/mg) when compared with the vehicle-treated group (132 pg/mg). However, no significant differences of orexin B were observed between groups. Additionally, no change was found in immobility tests.

  8. Immunotoxic effects of prolonged dietary exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Badesha, J S; Maliji, G; Flaks, B

    1995-12-07

    The effects of low level exposure of rats to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) on their immune system was investigated Dietary administration to young adult male Leeds strain rats of a total dose of 3 micrograms/kg body weight of TCDD resulted in an exposure duration-dependent reduction of in vitro lipopolysaccharide-induced production of interleukin (IL)-1 in cultures of their splenic macrophages. A 30-day exposure produced approximately 30% suppression and 180-day exposure produced approximately 52% suppression. This reduction did not negatively influence lipopolysaccharide- induced proliferation of B cells, instead an enhancement of B cell proliferation was observed after 30 days exposure. A 180 day exposure significantly suppressed the generation of IL-2 by either concanavalin A or phorbol myristate acetate/calcium ionophore stimulation, and reduced the lectin-induced proliferation of splenic T cells. The 30-day TCDD exposure showed no such immunotoxicity. TCDD at both exposure durations suppressed the expression of the alpha chain of the IL-2 receptor in concanavalin A-activated T cells, without affecting the CD4+/CD8+ ratio. The results suggest that exposure to a low dietary dose of TCDD suppresses the functions of several T cell subsets, some of the immunotoxic effects being produced early, while others require a longer exposure also down-regulates the IL-1 production function of macrophages. A common mechanism of TCDD immunotoxicity may be on the multifunctional signal transduction pathways downstream to the activation of protein kinase C and Ca2+ flux.

  9. Aryl hydrocarbon receptor activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs human B lymphopoiesis.

    PubMed

    Li, Jinpeng; Phadnis-Moghe, Ashwini S; Crawford, Robert B; Kaminski, Norbert E

    2017-03-01

    The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized. An in vitro B cell development model system was established by co-culturing human cord blood-derived HSCs with irradiated human primary bone marrow stromal cells. Using this in vitro model, we found that TCDD significantly suppressed the total number of hematopoietic stem and progenitor cells (HSPC) in a concentration-dependent manner. Cell death analysis demonstrated that the decrease in cell number was not due to cytotoxicity by TCDD. In addition, TCDD markedly decreased CD34 expression on HSPCs. Structure-activity relationship studies using dioxin congeners demonstrated a correlation between the relative AHR binding affinity and the magnitude of decrease in the number of HSPCs and CD34 expression, suggesting that AHR mediates the observed TCDD-elicited changes in HSPCs. Moreover, a significant reduction in lineage committed B cell-derived from HSCs was observed in the presence of TCDD, indicating impairment of human B cell development. Similar effects of TCDD were observed regardless of the use of stromal cells in cultures indicating a direct effect of TCDD on HSCs. Collectively, we demonstrate that AHR activation by TCDD on human HSCs impairs early stages of human B lymphopoiesis.

  10. Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts

    SciTech Connect

    Koskela, Antti; Viluksela, Matti; Keinänen, Meeri; Tuukkanen, Juha; Korkalainen, Merja

    2012-09-01

    The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6 J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1–10 nM TBT, 0.01–1 nM TCDD or 10 nM TBT + 1 nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption. -- Highlights: ► Combined exposure to TCDD and TBT evoked a unique gene expression profile. ► Osteoblast differentiation was synergistically disturbed after combined exposure. ► Bone resorbing activity was additively decreased after combined exposure.

  11. Long-term fate and bioavailability of sediment associated 2,3,7,8-tetrachlorodibenzofuran in littoral enclosures

    SciTech Connect

    Currie, R.S.; Fairchild, W.L.; Holoka, M.H.; Muir, D.C.G.

    2000-06-01

    the fate and bioavailability of 2,3,7,8-tetrachlorodibenzofuran (TCDF; 4,6-tritium labeled) was examined over a 3-year period in littoral enclosures in a small oligotrophic lake in the Experimental Lakes Area. Tetrachlorodibenzofuran was added as a single dose or as five small multiple additions over a 5-d period in a sediment slurry. Tetrachlorodibenzofuran was rapidly redistributed, mainly to bottom sediments reflecting removal on settling particles. Between 0 and 120 d. 80 to 90% of TCDF in the water column was associated with particles (>1 {micro}m). The highest concentration of TCDF in suspended particles was consistently observed in the smallest size fraction (0.22--1 {micro}m) at 326 to 464 d post treatment. Mode of addition had no effect on TCDF concentrations in water or surficial sediments or pore waters throughout the experiment. Mean TCDF concentrations in surficial sediment were 1.830 {+-} 1.180 pg/g whereas they averaged 1.260 {+-} 596 pg/g OC from 318 to 851 d post treatment. Increasing concentrations of TCDE in lower sediment layers at 952 d suggests that TCDF was either diffusing into the sediment or undergoing burial. Fugacity (f) calculations indicated that the TCDF in enclosures shifted from disequilibrium favoring the water column to a disequilibrium with respect to bottom sediments from day 21 onward. Initially, TCDF was more bioavailable to filtering and deposit feeders (mussels, Chironomidae, Hexagenia sp., and zooplankton) in enclosures receiving multiple additions; however, differences were rarely statistically significant. Concentrations of TCDF in all organisms were initially high, and they decreased in later sampling periods. Biota--sediment-accumulation factors (BSAFs) in mussels and crayfish were >1 in the early sampling periods, which reflected greater bioavailability of the added particle-borne TCDF. By 851 d, BSAFs had declined to 0.02 to 0.04, reflecting removal of TCDF from the water column and from surficial sediments.

  12. 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in extracts of Baltic white-tailed sea eagles

    SciTech Connect

    Koistinen, J.; Giesy, J.P.; Koivusaari, J.; Nuuja, I.; Vuorinen, P.J.; Paasivirta, J.

    1997-07-01

    Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin-(TCDD) equivalents were measured in extracts of Baltic white-tailed sea eagle tissues. Extracts of salmon, ringed seal, and grey seal were analyzed as other predatory species of the same area. Concentrations in eagle and seal tissues were greater than those in salmon. Concentrations of TCDD equivalents (TCDD-EQs) determined by the H4IIE bioassay were compared with toxic equivalents (TEQs) derived from instrumental chemical analyses in fractions containing polychlorinated dibenzo-P-dioxins and polychlorinated dibenzofurans (PCDD/PCDF) or coplanar polychlorinated biphenyls (PCBs). Toxic equivalents were calculated by use of an additive model in which the product of the concentrations of instrumentally measured individual congeners were multiplied by their TCDD equivalency factors and were summed to give a total concentration of TEQs. The TCDD-EQs were compared with TEQs to develop a mass balance to determine whether all the TCDD-like activity was accounted for. The TEQs determined by chemical analyses for coplanar PCBs was 770 pg/g fw, and that of PCDD/PCDFs was 270 pg/g fw in this eagle. Thus, concentrations of TCDD-EQs were approx. 20% greater than those of TEQs. The true difference in activities is probably greater because of lower recoveries and infra-additivities among congeners in the bioassay. This indicates that there are compounds present in the extracts that can contribute to the total concentrations of TCDD-EQs in white-tailed sea eagle eggs to the no-observable-adverse-effect concentration, ranged from 7.3 to 141. This indicates that current concentrations of TCDD-EQs in these eggs are likely causing adverse effects in the Baltic populations of white-tailed sea eagles. This study indicated that the H4IIE bioassay is useful for monitoring the presence and biological activity of TCDD-like compounds in environmental samples like white-tailed sea eagles.

  13. Pichia pastoris secretes recombinant proteins less efficiently than Chinese hamster ovary cells but allows higher space-time yields for less complex proteins.

    PubMed

    Maccani, Andreas; Landes, Nils; Stadlmayr, Gerhard; Maresch, Daniel; Leitner, Christian; Maurer, Michael; Gasser, Brigitte; Ernst, Wolfgang; Kunert, Renate; Mattanovich, Diethard

    2014-04-01

    Chinese hamster ovary (CHO) cells are currently the workhorse of the biopharmaceutical industry. However, yeasts such as Pichia pastoris are about to enter this field. To compare their capability for recombinant protein secretion, P. pastoris strains and CHO cell lines producing human serum albumin (HSA) and the 3D6 single chain Fv-Fc anti-HIV-1 antibody (3D6scFv-Fc) were cultivated in comparable fed batch processes. In P. pastoris, the mean biomass-specific secretion rate (qp ) was 40-fold lower for 3D6scFv-Fc compared to HSA. On the contrary, qp was similar for both proteins in CHO cells. When comparing both organisms, the mean qp of the CHO cell lines was 1011-fold higher for 3D6scFv-Fc and 26-fold higher for HSA. Due to the low qp of the 3D6scFv-Fc producing strain, the space-time yield (STY) was 9.6-fold lower for P. pastoris. In contrast, the STY of the HSA producer was 9.2-fold higher compared to CHO cells because of the shorter process time and higher biomass density. The results indicate that the protein secretion machinery of P. pastoris is much less efficient and the secretion rate strongly depends on the complexity of the recombinant protein. However, process efficiency of the yeast system allows higher STYs for less complex proteins.

  14. Primary peripheral T cells become susceptible to 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in vitro upon activation and in the presence of dendritic cells.

    PubMed

    Singh, Narendra P; Nagarkatti, Mitzi; Nagarkatti, Prakash

    2008-06-01

    Although the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cells in vivo have been well characterized, attempts to reproduce these findings in vitro have not been successful. In the current study, we examined whether activation or the presence of dendritic cells (DCs) would make primary naive T cells from C57BL/6 mice susceptible to TCDD-induced apoptosis in vitro. Although nonactivated primary T cells cultured with 10 to 1000 nM TCDD were relatively resistant to apoptosis, they became sensitive to apoptosis upon activation with concanavalin A (ConA). Moreover, ConA-activated T cells cultured in the presence of DCs showed highest levels of TCDD-induced apoptosis. Likewise, primary T cells from OT.II.2a mice cultured with specific ovalbumin peptide and syngeneic DCs showed higher levels of apoptosis compared with similar nonactivated T cells. T-cell activation led to up-regulation of aryl hydrocarbon receptor (AhR), Fas, and Fas-ligand (FasL) expression. In addition, DC maturation and culture with TCDD caused significant induction of FasL. TCDD-mediated apoptosis in activated peripheral T cells was AhR-dependent. Analysis of why nonactivated T cells are more resistant, whereas activated T cells are sensitive to TCDD-induced apoptosis revealed that TCDD treatment of activated but not nonactivated T cells led to down-regulation of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of apoptosis. Moreover, down-regulation of c-FLIP using small interfering RNA in nonactivated T cells made them sensitive to TCDD-induced apoptosis. The current study demonstrates for the first time that TCDD can induce apoptosis in vitro in peripheral T cells upon activation and in the presence of DCs and that this may be mediated by down-regulation of c-FLIP.

  15. Primary Peripheral T Cells Become Susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Mediated Apoptosis in Vitro upon Activation and in the Presence of Dendritic Cells

    PubMed Central

    Singh, Narendra P.; Nagarkatti, Mitzi; Nagarkatti, Prakash

    2009-01-01

    Although the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cells in vivo have been well characterized, attempts to reproduce these findings in vitro have not been successful. In the current study, we examined whether activation or the presence of dendritic cells (DCs) would make primary naive T cells from C57BL/6 mice susceptible to TCDD-induced apoptosis in vitro. Although nonactivated primary T cells cultured with 10 to 1000 nM TCDD were relatively resistant to apoptosis, they became sensitive to apoptosis upon activation with concanavalin A (ConA). Moreover, ConA-activated T cells cultured in the presence of DCs showed highest levels of TCDD-induced apoptosis. Likewise, primary T cells from OT.II.2a mice cultured with specific ovalbumin peptide and syngeneic DCs showed higher levels of apoptosis compared with similar nonactivated T cells. T-cell activation led to up-regulation of aryl hydrocarbon receptor (AhR), Fas, and Fas-ligand (FasL) expression. In addition, DC maturation and culture with TCDD caused significant induction of FasL. TCDD-mediated apoptosis in activated peripheral T cells was AhR-dependent. Analysis of why nonactivated T cells are more resistant, whereas activated T cells are sensitive to TCDD-induced apoptosis revealed that TCDD treatment of activated but not nonactivated T cells led to down-regulation of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of apoptosis. Moreover, down-regulation of c-FLIP using small interfering RNA in nonactivated T cells made them sensitive to TCDD-induced apoptosis. The current study demonstrates for the first time that TCDD can induce apoptosis in vitro in peripheral T cells upon activation and in the presence of DCs and that this may be mediated by down-regulation of c-FLIP. PMID:18334599

  16. Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

    PubMed

    Beranek, Martin; Fiala, Zdenek; Kremlacek, Jan; Andrys, Ctirad; Hamakova, Kvetoslava; Chmelarova, Marcela; Palicka, Vladimir; Borska, Lenka

    2016-07-25

    Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

  17. Ultrafast excited-state dynamics and vibrational cooling of 8-oxo-7,8-dihydro-2'-deoxyguanosine in D2O.

    PubMed

    Zhang, Yuyuan; Dood, Jordan; Beckstead, Ashley; Chen, Jinquan; Li, Xi-Bo; Burrows, Cynthia J; Lu, Zhen; Matsika, Spiridoula; Kohler, Bern

    2013-12-05

    Nguyen and Burrows recently demonstrated that UV-B irradiation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a signature product of oxidatively damaged DNA, can repair cyclobutane pyrimidine dimers in double-stranded DNA (J. Am. Chem. Soc. 2011, 133, 14586 - 14589). In order to test the hypothesis that repair occurs by photoinduced electron transfer, it is critical to determine basic photophysical parameters of 8-oxodG including the excited-state lifetime. Here, femtosecond transient absorption spectroscopy was used to study the ultrafast excited-state dynamics of 8-oxodG with excitation in the UV and probing at visible and mid-IR wavelengths. The excited-state lifetimes of both neutral and basic forms of 8-oxodG in D2O are reported for the first time by monitoring the disappearance of excited-state absorption at 570 nm. The lifetime of the first excited state of the neutral form is 0.9 ± 0.1 ps, or nearly twice as long as that of 2'-deoxyguanosine. The basic form of 8-oxodG exhibits a much longer excited-state lifetime of 43 ± 3 ps. Following ultrafast internal conversion by neutral 8-oxodG, a vibrationally hot ground state is created that dissipates its excess vibrational energy to the solvent on a time scale of 2.4 ± 0.4 ps. Femtosecond time-resolved IR experiments provide additional insights into excited-state dynamics and the vibrational relaxation of several modes in the fingerprint region.

  18. Activation of muscular TrkB by its small molecular agonist 7,8-dihydroxyflavone sex-dependently regulates energy metabolism in diet-induced obese mice.

    PubMed

    Chan, Chi Bun; Tse, Margaret Chui Ling; Liu, Xia; Zhang, Shuai; Schmidt, Robin; Otten, Reed; Liu, Liegang; Ye, Keqiang

    2015-03-19

    Chronic activation of brain-derived neurotrophic factor (BDNF) receptor TrkB is a potential method to prevent development of obesity, but the short half-life and nonbioavailable nature of BDNF hampers validation of the hypothesis. We report here that activation of muscular TrkB by the BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is sufficient to protect the development of diet-induced obesity in female mice. Using in vitro and in vivo models, we found that 7,8-DHF treatment enhanced the expression of uncoupling protein 1 (UCP1) and AMP-activated protein kinase (AMPK) activity in skeletal muscle, which resulted in increased systemic energy expenditure, reduced adiposity, and improved insulin sensitivity in female mice fed a high-fat diet. This antiobesity activity of 7,8-DHF is muscular TrkB-dependent as 7,8-DHF cannot mitigate diet-induced obesity in female muscle-specific TrkB knockout mice. Hence, our data reveal that chronic activation of muscular TrkB is useful in alleviating obesity and its complications.

  19. Molecular characterization of mutation and comparison of mutation profiles in the hprt gene of Chinese hamster ovary cells treated with benzo[a]pyrene trans-7,8-diol-anti-9,10-epoxide, 1-nitrobenzol[a]pyrene trans-7,8-diol-anti-9,10-epoxide, and 3-nitrobenzol[a]pyrene trans-7,8-diol-anti-9,10-epoxide

    SciTech Connect

    Zhan, D.J.; Heflich, R.H.; Fu, P.P.

    1996-12-31

    Both 1- and 3-nitrobenzol[a] pyrene (nitro-BaP) are environmental contaminants, potent mutagens in Salmonella, and moderate mutagens in Chinese hamster ovary (CHO) cells. The mutagenicity of their oxidized metabolites, trans-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydro-1-nitrobenzol[a]pyrene (1-nitro-BaP-DE) and trans-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo[a]pyrene (3-nitro-BaP-DE), together with trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzol[a]pyren (BaP-DE), was determined in CHO-K1 cells, and the resulting mutations at the hprt locus were characterized by polymerase chain reaction (PCR) amplification of reverse-transcribed hprt mRNA, followed by DNA sequence analysis. The mutant frequencies, in mutants/10{sup 6} clonable cells, at 30 and 100 ng/ml, were BaP-DE, 248 and 456; 1-nitro-BaP-DE, 68 and 260; 3-nitro-BaP-DE, 81 and 232, respectively. In general, the three diolepoxides exhibited similar mutational spectra: (1) 64% (23/36 sequenced mutants) of BaP-DE, 53% (19/36) of 1-nitro-BaP-DE, and 64% (23/36) of 3-nitro-BaP-DE mutants resulted from simple base pair substitution, with the predominant mutation being G{r_arrow}T transversion: (2) 90%, 100%, and 100% of mutations at G:C had the mutated dG on the nontranscribed DNA strand; and (3) about one quarter of the mutants produced by each mutagen had one or more PCR products with partial or complete exon deletions. 61 refs., 1 fig., 7 tabs.

  20. Hanford Tank Safety Project: Minutes of the Tank Waste Science Panel meeting, February 7--8, 1991

    SciTech Connect

    Strachan, D.M.

    1991-06-01

    The Tank Waste Science Panel met February 7--8, 1991, to review the latest data from the analyses of the October 24, 1990, gas release from Tank 241-SY-101 (101-SY) at Hanford; discuss the results of work being performed in support of the Hanford Tank Safety Project; and be briefed on the ferrocyanide issues included in the expanded scope of the Science Panel. The shapes of the gas release curves from the past three events are similar and correlate well with changes in waste level, but the correlation between the released volume of gas and the waste height is not as good. An analysis of the kinetics of gas generation from waste height measurements in Tank 101-SY suggests that the reaction giving rise to the gases in the tank is independent of the gas pressure and independent of the physical processes that give rise to the episodic release of the gases. Tank waste height data were also used to suggest that a floating crust formed early in the history of the tank and that the current crust is being made thicker in the eastern sector of the tank by repeated upheaval of waste slurry onto the surface. The correlation between the N{sub 2}O and N{sub 2} generated in the October release appears to be 1:1, suggesting a single mechanistic pathway. Analysis of other gas generation ratios, however, suggests that H{sub 2} and N{sub 2}O are evolved together, whereas N{sub 2} is from the air. If similar ratios are observed in planned radiolysis experiments are Argonne National Laboratory, radiolysis would appear to be generating most of the gases in Tank 101-SY. Data from analysis of synthetic waste crust using a dynamic x-ray diffractometer suggest that, in air, organics are being oxidized and liberating CO{sub 2} and NO{sub x}. Experiments at Savannah River Laboratory indicate that irradiation of solutions containing NO{sub 3} and organics can produce N{sub 2}O.

  1. Development, characterization, and biological properties of meningococcal immunotype L3,7,(8),9-specific monoclonal antibodies.

    PubMed Central

    Verheul, A F; Kuipers, A J; Braat, A K; Dekker, H A; Peeters, C C; Snippe, H; Poolman, J T

    1994-01-01

    In this study, we characterize the properties of nine monoclonal antibodies (MAbs) that recognize meningococcal lipopolysaccharides (LPS). The following three specific MAbs that had not been described previously were elicited in BALB/c mice by using an immunotype L3,7,9 oligosaccharide-tetanus toxoid conjugate in combination with Quil A: 4D1-B3, 3A12-E1, and 4A8-B2. These MAbs reacted with L3,7,9 LPS on immunoblots and in the LPS enzyme-linked immunosorbent assay (ELISA) and recognised strains containing L3, L3,7, L8 (except 3A12-E1), or L9 LPS in the whole-cell ELISA. The six other MAbs have been described in previous studies (K. Saukkonen, M. Leinonen, H. Abdillahi, and J.T. Poolman, Vaccine 7:325-328, 1989; R.J.P.M. Scholten, B. Kuipers, H.A. Valkenburg, J. Danjert, W.D. Zollinger, and J.T. Poolman, J. Med. Microbiol., in press) and were obtained after immunization with outer membrane protein complexes containing LPS: MN15A11, MN15A8-1, MN15A17-1, MN11A11G, MN14F20-11, and MN14F21-11. MN15A11 was specific for L3,7,9 LPS and displayed properties similar to those of 3A12-E1. MN15A17-1, MN14F20-1, and MN11A11G were cross-reactive, and MN14F21-11 was specific for the L1,8 immunotype. Epitope specificities of MAbs reacting with L3,7,(8),9 strains were analyzed. MAbs 4D1-B3, 3A12-E1, and 4A8-B2 recognized phosphoethanolamine group-containing oligosaccharide-specific epitopes. MN15A11 and MN15A17-1 were probably directed against a conformational epitope, although for MN5A11 recognition of an unknown L3,7,9-specific epitope in the 2-keto-3-deoxyoctulosonic acid (KDO)-lipid A region cannot be excluded. MN15A8-1, a strongly cross-reactive MAb, recognized a determinant which included the KDO-lipid A region and the more terminal saccharides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8556528

  2. Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal.

    PubMed

    Silkworth, J B; Cutler, D S; Sack, G

    1989-02-01

    The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm). The results suggest that the immunosuppression caused by OPL in BALB/cByJ mice was primarily due to TCDD, that the non-TCDD components of OPL diminished the TCDD immunotoxicity in the DBA/2J strain, and that the thymic atrophy and hepatomegaly were caused primarily by the non

  3. Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

    SciTech Connect

    Silkworth, J.B.; Cutler, D.S.; Antrim, L.; Houston, D.; Tumasonis, C.; Kaminsky, L.S. )

    1989-07-01

    The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups.

  4. Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

    SciTech Connect

    Silkworth, J.B.; Cutler, D.S.; Sack, G.

    1989-02-01

    The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm).

  5. A Mini-Megathrust Event in an Incipient Subduction Zone: The 2012 Mw 7.8 Haida Gwaii Earthquake Sequence

    NASA Astrophysics Data System (ADS)

    Farahbod, A.; Kao, H.; Shan, S.

    2013-12-01

    The 2012 Haida Gwaii earthquake (Mw 7.8) is the largest event recorded by modern seismograph networks in Canada. The source region is associated with a complicated tectonic system that constitutes the boundary between the North America and Pacific plates. In addition to the strike-slip Queen Charlotte Fault located immediately offshore west of the Haida Gwaii island, the oblique convergence between the two plates also create an incipient subduction zone that is confirmed by previous seismic velocity studies. In this study, we systematically examine the seismic waveforms of the Haida Gwaii earthquake sequence as recorded by the Canadian National Seismograph Network (CNSN) stations. Because of the sparse station density in the source region, precise determination of earthquake hypocenters is challenging. We add the information of back-azimuth and incident angle, both are derived from the cross-correlation of 3-component waveforms, into the locating process to better constrain the distribution of aftershocks. For the first 24 hours, we are able to locate 264 aftershock events whereas the routine location catalogue gives only 106 events. The corresponding b-value is 0.56 with a magnitude of completeness of 2.3. The main shock shows low-angle thrust focal mechanism with the slip consistent in the direction of relative convergence. The distribution of aftershocks forms two major clusters. One is directly updip from the main rupture zone but within the subducting Pacific plate. Focal mechanisms of events with Mw >= 4.5 in this cluster are mostly normal-faulting, probably in response to plate bending. The other cluster is located within the overriding crust of the North America plate. These events show a mixture of normal and strike-slip faulting. Few aftershocks occurred on the main rupture zone, but were all too small for moment-tensor inversion. Most events within the down-going slab beneath the plate interface show downdip extensional mechanisms. We have not observed

  6. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to embryos of the fathead minnow (Pimephales promelas, Rafinesque)

    SciTech Connect

    Olivieri, C.; Cooper, K.

    1995-12-31

    This study correlates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) residue and its toxicity to the fathead minnow embryo exposed to levels lower than the TCDD solubility range. The TCDD tissue doses in the embryo/larvae were related to gross lesions, delayed hatching, and death. A 7-day bioconcentration factor on a lipid basis (BCF{sub L}) was calculated. Embryos at the blatsula stage were exposed to [{sup 3}H] TCDD water concentrations (0.37, 0.59, 1.2, 2.83, and 10.1 6 ng/L), a nontreatment control and a solvent carrier control. Lesions were qualified as mild and severe based on their onset and their pathogenesis. Thus, mild lesions developed just prior to hatching or post-hatching at the fifth day of development. The severe lesions appeared at the third day of development. Embryos with tissue doses {le}2.46 {+-} 1.34 ng/g consistently developed mild lesions, while embryos with tissue doses {ge} 12.07 {+-} 4.91 ng/g developed severe lesions. The lowest observable adverse effect level was 0.04 {+-} 0.02 ng/g. The calculated 7-day ED{sub 50} was 0.14 ng/g. There was no delayed hatching at any of the concentrations tested. Embryo death occurred at a tissue concentration {ge}2.46 ng/g. The calculated 7-day LD{sub 50} was 25.71 ng/g. The relationship between the concentration of TCDD in the water (x = ng/L) and in the tissue dose (y = ng/g) fitted a linear curve y = {minus}1,143 + 3,792.5x, r{sup 2} = 0.98. The calculated BCF{sub L} (wet weight) was dose dependent. Embryos with tissue doses of 0.04 and 0.16 ng/g had BCF{sub L} of 2,700 and 3,325, respectively. Embryos with tissue doses of 2.46, 12.07, and 37.07 ng/g, had a BCF{sub L} of 104,225, 106,625 and 91,075, respectively.

  7. Different sensitization profile for asthma, rhinitis, and eczema among 7-8-year-old children: report from the Obstructive Lung Disease in Northern Sweden studies.

    PubMed

    Rönmark, Eva; Perzanowski, Matthew; Platts-Mills, Thomas; Lundbäck, Bo

    2003-04-01

    Sensitization to different airborne allergens in relation to asthma, rhinitis, and eczema has been studied. A cross-sectional study was performed among 7-8-year-old children living in northern Sweden. The ISAAC-questionnaire with additional questions were sent to the parents, and 3431 (97%) participated. Two-thirds of the children were invited to undergo a skin test with 10 common airborne allergens, and 2148 (88%) participated. The prevalence rates of all three diseases were significantly higher among the children who were sensitized to any of the tested allergens. Among asthmatics, 40% were sensitized to cat, 34% to dog, 28% to horse, 23% to birch and 16% to timothy. The corresponding figures for rhinitis were: cat 49%, dog 33%, horse 37%, birch 46%, timothy 32%; and for eczema: cat 29%, dog 21%, horse 15%, birch 20%, and timothy 11%. Only a few children were sensitized to mites or moulds. The main risk factors for all three diseases were type-1 allergy and a family history of the disease. Independently from other risk factors, sensitization to dog (OR 2.4) and horse (OR 2.2) were significant risk factors for asthma. Sensitization to birch (OR 6.0), horse (OR 4.1), and timothy (OR 2.8) were significant risk factors for rhinitis, while birch (OR 2.4), dog (OR 2.0) and cat (OR 1.6) were significant risk factors for eczema. Despite a large over-lapping of the diseases the pattern of sensitization was different for asthma, rhinitis and eczema. Sensitization to cat was most common among all children, but sensitization to dog and horse was associated with the highest risk for asthma, and sensitization to birch showed the highest risk for rhinitis and eczema. The different risk factor pattern for the often coexisting diseases; asthma, rhinitis, and eczema, may indicate differences in the etiology.

  8. Hyperoxia depletes (6R)-5,6,7,8-tetrahydrobiopterin levels in the neonatal retina: implications for nitric oxide synthase function in retinopathy.

    PubMed

    Edgar, Kevin S; Matesanz, Nuria; Gardiner, Tom A; Katusic, Zvonimir S; McDonald, Denise M

    2015-06-01

    Retinopathy of prematurity is a sight-threatening complication of premature birth caused by nitro-oxidative insult to the developing retinal vasculature during therapeutic hyperoxia exposure and later ischemia-induced neovascularization on supplemental oxygen withdrawal. In the vasodegenerative phase, during hyperoxia, defective endothelial nitric oxide synthase (NOS) produces reactive oxygen and nitrogen free radicals rather than vasoprotective nitric oxide for unclear reasons. Crucially, normal NOS function depends on availability of the cofactor (6R)-5,6,7,8-tetrahydrobiopterin (BH4). Because BH4 synthesis is controlled enzymatically by GTP cyclohydrolase (GTPCH), we used GTPCH-depleted mice [hyperphenylalaninemia strain (hph1)] to investigate the impact of hyperoxia on BH4 bioavailability and retinal vascular pathology in the neonate. Hyperoxia decreased BH4 in retinas, lungs, and aortas in all experimental groups, resulting in a dose-dependent decrease in NOS activity and, in the wild-type group, elevated NOS-derived superoxide. Retinal dopamine levels were similarly diminished, consistent with the dependence of tyrosine hydroxylase on BH4. Despite greater depletion of BH4, the hph(+/-) and hph1(-/-) groups did not show exacerbated hyperoxia-induced vessel closure, but exhibited greater vascular protection and reduced progression to neovascular disease. This vasoprotective effect was independent of enhanced circulating vascular endothelial growth factor (VEGF), which was reduced by hyperoxia, but to local retinal ganglion cell layer-derived VEGF. In conclusion, a constitutively higher level of VEGF expression associated with retinal development protects GTPCH-deficient neonates from oxygen-induced vascular damage.

  9. Urea lesion formation in DNA as a consequence of 7,8-dihydro-8-oxoguanine oxidation and hydrolysis provides a potent source of point mutations.

    PubMed

    Henderson, Paul T; Neeley, William L; Delaney, James C; Gu, Feng; Niles, Jacquine C; Hah, Sang Soo; Tannenbaum, Steven R; Essigmann, John M

    2005-01-01

    The DNA oxidation product 7,8-dihydro-8-oxoguanine (8-oxoG) forms several mutagenic oxidation products, including a metastable oxaluric acid (Oa) derivative. We report here that a synthetic oligonucleotide containing Oa hydrolyzes under simulated "in vivo" conditions to form a mutagenic urea (Ua) lesion. Using the Oa 2'-deoxyribonucleoside as a model, the hydrolysis rate depended strongly upon the concentrations of bicarbonate and divalent magnesium. In buffered solutions containing physiologically relevant levels of these species, the half-life of Oa nucleoside was approximately 40 h at 37 degrees C. The mutagenic properties of Ua in DNA were investigated using a M13mp7L2 bacteriophage genome containing Ua at a specific site. Transfection of the lesion-containing genome into wild-type AB1157 Escherichia coli allowed determination of the mutation frequency and DNA polymerase bypass efficiency from the resulting progeny phage. Ua was bypassed with an efficiency of 11% as compared to a guanine control and caused a 99% G-->T mutation frequency, assuming the lesion originated from G, which is at least an order of magnitude higher than the mutation frequency of 8-oxoG under the same conditions. SOS induction of bypass DNA polymerase(s) in the bacteria prior to transfection caused the mutation frequency and type to shift to 43% G-->T, 46% G-->C, and 10% G-->A mutations. We suggest that Ua is instructional, meaning that the shape of the lesion and its interactions with DNA polymerases influence which nucleotide is inserted opposite the lesion during replication and that the instructional nature of the lesion is modulated by the size of the binding pocket of the DNA polymerase. Replication past Ua, when formed by hydrolysis of the 8-oxoG oxidation product Oa, denotes a pathway that nearly quantitatively generates point mutations in vivo.

  10. Diet quality of U.K. infants is associated with dietary, adiposity, cardiovascular, and cognitive outcomes measured at 7-8 years of age.

    PubMed

    Golley, Rebecca K; Smithers, Lisa G; Mittinty, Murthy N; Emmett, Pauline; Northstone, Kate; Lynch, John W

    2013-10-01

    Whereas the influence of pregnancy diet and milk feeding on children's health and development is well characterized, the role of early food intake and eating behaviors is largely unexplored. This study aimed to determine whether the degree of adherence to complementary feeding guidelines was associated with dietary, obesity, cardiovascular, and cognitive outcomes at 7-8 y of age. Data were analyzed from the Avon Longitudinal Study of Parents and Children using parent-completed dietary questionnaires at 6 mo of age to calculate a Complementary Feeding Utility Index score. Regression analysis was used to explore associations between the index score and dietary patterns derived via principal component analysis (n = 4326), body-mass index (BMI) (n = 4801), waist circumference (n = 4798), blood pressure (n = 4685), and lipids (n = 3232) measured at age 7 y; and intelligence quotient (IQ) measured at age 8 y (n = 4429) after adjustment for covariates. The index score was negatively associated with a "processed" dietary pattern (β = -0.16; 95% CI: -0.20, -0.13; P < 0.001) but positively associated with a "health conscious" dietary pattern [β = 0.18 (95% CI: 0.14, 0.21); P < 0.001]. A higher index score was also positively associated with total, verbal, and performance IQ scores at 8 y of age [β = 1.92 (95%CI: 1.38, 2.47); P < 0.001 for total IQ). The index score was weakly associated with waist circumference [β = -0.15 (95%CI: -0.31, -0.002); P = 0.046] and diastolic blood pressure [β = -0.24 (95%CI: -0.47, -0.01); P = 0.043] at 7 y of age but was not associated with BMI or other cardiovascular risk factors. These findings suggest that adherence to current complementary feeding guidelines may have implications for some, but not all, health and development outcomes in childhood.

  11. Protective effects of (6R)-5,6,7,8-tetrahydro-l-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva

    PubMed Central

    Tanaka, Yusaku; Toyama, Toshizo; Wada-Takahashi, Satoko; Sasaki, Haruka; Miyamoto, Chihiro; Maehata, Yojiro; Yoshino, Fumihiko; Yoshida, Ayaka; Takahashi, Shun-suke; Watanabe, Kiyoko; Lee, Masaichi-Chang-il; Todoki, Kazuo; Hamada, Nobushiro

    2016-01-01

    We herein investigated the regulatory mechanism in the circulation responsible for rat gingival reactive hyperemia (RH) associated with ischemia/reperfusion (I/R). RH was analyzed using a laser Doppler flowmeter. RH and I/R were elicited by gingival compression and release with a laser Doppler probe. RH increased in a time-dependent manner when the duration of compression was between 30 s and 20 min. This increase was significantly suppressed by Nω-nitro-l-arginine-methyl-ester (l-NAME), 7-nitroindazole (7-NI), and 2,4-diamino-6-hydroxypyrimidine (DAHP). However, RH was markedly inhibited following 60 min of compression. This inhibition was significantly decreased by treatments with superoxide dismutase (SOD), (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4), and sepiapterin. The luminescent intensity of superoxide anion (O2•−)-induced 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo-[1,2-a] pyrazine-3-one (MCLA) was markedly decreased by SOD and BH4, but only slightly by sepiapterin. BH4 significantly decreased O2•− scavenging activity in a time-dependent manner. These results suggested that nitric oxide (NO) secreted by the nitrergic nerve played a role in regulating local circulation in rat gingiva. This NO-related regulation of local circulation was temporarily inhibited in the gingiva by the I/R treatment. The decrease observed in the production of NO, which was caused by suppression of NO synthase (NOS) activity subsequent to depletion of the NOS co-factor BH4 by O2•−, played a partial role in this inhibition. PMID:26798200

  12. 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD) induces premature senescence in human and rodent neuronal cells via ROS-dependent mechanisms.

    PubMed

    Wan, Chunhua; Liu, Jiao; Nie, Xiaoke; Zhao, Jianya; Zhou, Songlin; Duan, Zhiqing; Tang, Cuiying; Liang, Lingwei; Xu, Guangfei

    2014-01-01

    The widespread environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent toxicant that causes significant neurotoxicity. However, the biological events that participate in this process remain largely elusive. In the present study, we demonstrated that TCDD exposure triggered apparent premature senescence in rat pheochromocytoma (PC12) and human neuroblastoma SH-SY5Y cells. Senescence-associated β-galactosidase (SA-β-Gal) assay revealed that TCDD induced senescence in PC12 neuronal cells at doses as low as 10 nM. TCDD led to F-actin reorganization and the appearance of an alternative senescence marker, γ-H2AX foci, both of which are important features of cellular senescence. In addition, TCDD exposure altered the expression of senescence marker proteins, such as p16, p21 and p-Rb, in both dose- and time-dependent manners. Furthermore, we demonstrated that TCDD promotes mitochondrial dysfunction and the accumulation of cellular reactive oxygen species (ROS) in PC12 cells, leading to the activation of signaling pathways that are involved in ROS metabolism and senescence. TCDD-induced ROS generation promoted significant oxidative DNA damage and lipid peroxidation. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular oxidative damage and neuronal senescence. Moreover, we found that TCDD induced a similar ROS-mediated senescence response in human neuroblastoma SH-SY5Y cells. In sum, these results demonstrate for the first time that TCDD induces premature senescence in neuronal cells by promoting intracellular ROS production, supporting the idea that accelerating the onset of neuronal senescence may be an important mechanism underlying TCDD-induced neurotoxic effects.

  13. Protective effects of (6R)-5,6,7,8-tetrahydro-l-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva.

    PubMed

    Tanaka, Yusaku; Toyama, Toshizo; Wada-Takahashi, Satoko; Sasaki, Haruka; Miyamoto, Chihiro; Maehata, Yojiro; Yoshino, Fumihiko; Yoshida, Ayaka; Takahashi, Shun-Suke; Watanabe, Kiyoko; Lee, Masaichi-Chang-Il; Todoki, Kazuo; Hamada, Nobushiro

    2016-01-01

    We herein investigated the regulatory mechanism in the circulation responsible for rat gingival reactive hyperemia (RH) associated with ischemia/reperfusion (I/R). RH was analyzed using a laser Doppler flowmeter. RH and I/R were elicited by gingival compression and release with a laser Doppler probe. RH increased in a time-dependent manner when the duration of compression was between 30 s and 20 min. This increase was significantly suppressed by N (ω)-nitro-l-arginine-methyl-ester (l-NAME), 7-nitroindazole (7-NI), and 2,4-diamino-6-hydroxypyrimidine (DAHP). However, RH was markedly inhibited following 60 min of compression. This inhibition was significantly decreased by treatments with superoxide dismutase (SOD), (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4), and sepiapterin. The luminescent intensity of superoxide anion (O2 (•-))-induced 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo-[1,2-a] pyrazine-3-one (MCLA) was markedly decreased by SOD and BH4, but only slightly by sepiapterin. BH4 significantly decreased O2 (•-) scavenging activity in a time-dependent manner. These results suggested that nitric oxide (NO) secreted by the nitrergic nerve played a role in regulating local circulation in rat gingiva. This NO-related regulation of local circulation was temporarily inhibited in the gingiva by the I/R treatment. The decrease observed in the production of NO, which was caused by suppression of NO synthase (NOS) activity subsequent to depletion of the NOS co-factor BH4 by O2 (•-), played a partial role in this inhibition.

  14. In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effects on fetal and adult cardiac gene expression and adult cardiac and renal morphology.

    PubMed

    Aragon, Andrea C; Kopf, Phillip G; Campen, Matthew J; Huwe, Janice K; Walker, Mary K

    2008-02-01

    The mouse heart is a target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during fetal development, and microarray analysis demonstrates significant changes in expression of cardiac genes involved in extracellular matrix (ECM) remodeling. We tested the hypothesis that developmental TCDD exposure would disrupt cardiac ECM expression and be associated with changes in cardiac morphology in adulthood. In one study, time-pregnant C57BL/6 mice were dosed with corn oil or 1.5, 3.0, or 6.0 microg TCDD/kg on gestation day (GD) 14.5 and sacrificed on GD 17.5, when changes in fetal cardiac mRNA expression were analyzed using quantitative PCR. TCDD induced mRNA expression of genes associated with ECM remodeling (matrix metalloproteinase 9 and 13, preproendothelin-1 [preproET-1]), cardiac hypertrophy (atrial natriuretic peptide, beta-myosin heavy chain, osteopontin), and aryl hydrocarbon receptor (AHR) activation (cytochrome P4501A1, AHR repressor). Further, all TCDD-induced changes required the AHR since gene expression was not altered in AHR knockout fetuses. In a second study, time-pregnant mice were treated with corn oil or 6.0 microg TCDD/kg on GD 14.5, and male offspring were assessed for changes in cardiac gene expression and cardiac and renal morphology at 3 months. All TCDD-induced changes in cardiac gene expression observed fetally, except for preproET-1, remained induced in the hearts of adult male offspring. Adult male offspring of TCDD-exposed dams also displayed cardiac hypertrophy, decreased plasma volume, and mild hydronephrosis. These results demonstrate that in utero and lactational TCDD exposures alter cardiac gene expression and cardiac and renal morphology in adulthood, which may increase the susceptibility to cardiovascular dysfunction.

  15. 2,3,7,8-tetrachlorodibenzo-p-dioxin: examination of biochemical effects involved in the proliferation and differentiation of XB cells

    SciTech Connect

    Knutson, J.C.; Poland, A.

    1984-10-01

    XB, a cell line derived form a mouse teratoma, differentiates into stratified squamous epithelium when incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). To examine the mediators of this response the effects produced by TCDD and those elicited by other compounds which stimulated epidermal proliferation and/or differentiation in mice were compared, XB/3T3 cultures keratinize when incubated with cholera toxin, epidermal growth factor (EGF), or TCDD , but not 12-0-tetradecanoylphorbol-13-acetate (TPA). Incubation of XB cells with TCDD for 48 hours produces an increase in thymidine incorporation, a response which is neither as large nor as rapid as that produced by cholera toxin, TPA, or EGF. Although both cholera toxin and TCDD stimulate differentiation and thymidine incorporation in XB/3T3 cultures, cholera toxin increases cAMP 30-fold in these cells, while TCDD does not affect cAMP accumulation. Inhibitors of arachidonic acid metabolism, which block epidermal proliferative responses to TPA in vivo, do not prevent the differentiation of XB cells in response to TCDD. In XB/3T3 cultures, TPA stimulates arachidonic acid release at all times tested (1,6, and 24 hours) and increases the incorporation of /sup 32/P/sub i/ into total phospholipids and phosphatidyl-choline after 3 hours. In contrast, D affects neither arachidonic acid release nor the turnover of phosphatidylinositol, or phosphatidylcholine at any of the times tested. Although biochemical effects which have been suggested as part of the mechanism of TCDD and produced by other epidermal proliferative compounds in XB cells were examined, no mediator of the TCDD-produced differentiation of XB/3T3 cultures was observed.

  16. In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

    DOE PAGES

    Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree; ...

    2017-01-21

    Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase Imore » metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in this paper in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 μM), and higher intrinsic clearance at lower substrate concentrations (<0.07 μM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Finally, kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.« less

  17. 2,3,7,8-Substituted PCDDs and PCDFs in sea lion (Otaria flavescens) skin biopsies from two South-western Atlantic populations.

    PubMed

    Jimènez, B; Gonzàlez, M J; Hernández, L M; Eljarrat, E; Rivera, J; Fossi, M C

    1999-02-01

    Congener specific 2,3,7,8-chlorinated PCDDs and PCDFs were determined in skin biopsies taken from sea lions (Otaria flavescens) living in two areas of the South-western Atlantic on the coast of Argentina (Mar del Plata and Punta Bermeja). This is the first report on PCDDs and PCDFs in sea lion skin biopsies from the southern hemisphere. Differences were found in the congener pattern according to the sampling area. Animals living in the polluted area (Mar del Plata harbour) had detectable levels of all seventeen 2,3,7,8-substituted congeners. Sea lions living in a control environment (Punta Bermeja, Patagonia) only exhibited 5 detectable congeners out of all seventeen 2,3,7,8-substituted congeners. However, total levels were low in both colonies studied. These data are consistent with previous work which has indicated that dioxins occur at relatively low levels in marine mammals, possibly due to rapid catabolism or elimination.

  18. Induction of CYP1A and ABC transporters in European sea bass (Dicentrarchus labrax) upon 2,3,7,8-TCDD waterborne exposure.

    PubMed

    Della Torre, Camilla; Mariottini, Michela; Vannuccini, Maria Luisa; Trisciani, Anna; Marchi, Davide; Corsi, Ilaria

    2014-08-01

    The aim of this study was to characterize the responsiveness of CYP1A and ABC transport proteins in European Sea bass (Dicentrarchus labrax) waterborne exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) (46 pg/L) for 24 h and 7 days. Genes modulation (abcb1, abcc1-2, cyp1a), EROD activity were investigated in liver and 2,3,7,8-TCDD bioconcentration in liver and muscle. TCDD induced significantly cyp1a gene expression and EROD activity at 24 h and 7 d. A significant up-regulation of abcb1 was also observed but only after 7 days. No modulation of abcc1 and abcc2 genes was observed. Waterborne TCDD exposure was able to induce CYP1A and abcb1 encoding for P-glycoprotein in juvenile of European sea bass.

  19. Systematic Detections of Early Aftershocks and Remotely Triggered Seismicity in China Following the 2015 Mw7.8 Gorkha, Nepal earthquake

    NASA Astrophysics Data System (ADS)

    Wu, J.; Peng, Z.; Yao, D.; LI, L.; Meng, X.; Wang, B.; Wang, W.; Li, C.

    2015-12-01

    The 2015/04/25 Mw7.8 Gorkha, Nepal earthquake occurred beneath the central portion of the Himalayan Frontal Thrust Fault. The mainshock was followed by numerous aftershocks near its epicentral region, as well as many earthquakes at various distances in China. Small to moderate-size earthquakes in Chongqing (~2500 km) and around Fangshan Pluton near Beijing (~3500 km) coincided with the arrivals of surface wave train, suggesting that they were likely triggered by dynamic stresses from the passing surface waves. 3 hours later, a M5.8 normal-faulting earthquake in Southern Tibet. Because of their close distances (within two fault-rupture lengths), it is not clear whether the M5.8 Tibetan event is triggered by static or dynamic stresses. Here we conduct a systematic detection of microseismicity in Nepal and Southern Tibet around the Nepal mainshock. We use earthquakes listed in the Advance National Seismic Network (ANSS) and China Earthquake Network Center (CENC) catalogs as templates, and scan through continuous waveform data within 700 km of the Nepal mainshock to detect additional smaller events that were not listed in these catalogs. As was done before, we apply a 0.5 to 8 Hz band-pass filter to both the template and continuous waveform data, and detect events with mean cross-correlation (CC) values that are at least 12 times larger than the daily median absolute deviation (MAD) values. Overall we have detected 5 times more aftershocks, as well as more than 80 uncatalogued events in Southern Tibet near the epicentral region of the M5.8 event. We also compute the dynamic and static stress changes on the two nodal planes of the M5.8 event. While we cannot completely rule out the influence of static stress change (because the M5.8 event is in the positive Coulomb stress change region), the amplitude of the dynamic stress change is several times larger than the static stress change, suggesting that this event is possibly triggered by dynamic stress changes (albeit with

  20. Love Canal Emergency Declaration Area habitability study. Volume 4. Soil assessment: 2,3,7,8-TCDD (tetrachlorodibenzo-p-dioxin). Final report

    SciTech Connect

    Not Available

    1988-03-01

    Environmental studies were conducted to provide data that could be used by the Commissioner of Health for the State of New York in determining whether the Emergency Declaration Area (EDA) surrounding the Love Canal hazardous-waste site is habitable. A soil assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was conducted to determine whether the soil in the EDA contains 2,3,7,8-TCDD at levels above the level of concern set by the Centers for Disease Control: 1.0 ppb. Samples of surface soil were collected at 2,274 locations throughout the EDA.

  1. 2.3.7.8-Tetrachlorodibenzo-p-Dioxin Induced Immunosuppression: Its Possible Alteration by In Vivo Administration of Specific Hepatic Enzyme Inducers.

    DTIC Science & Technology

    1987-06-27

    England .2 LIST OF ACOREVIAT:CNS AND SYMBOLS TCDD =2.3.7.8-tetrachlorodibenzo-p-dioxtn TCDF = 2.3.7 8-IOetrachlo’dibenzofuran 3MC =3-methyicholanthrene...this research program was to clarify whether drugs that in vitro inhibit TCDD binding to the hepatic cytosolic Ah "rec3ptor" such as 3MC , PNF and TCDF...these enzymes has also been performed. The study of this year has been concentrated on the effects of only two inducers, that is TCDF and 3MC , since

  2. Game Times and Higher Winning Percentages of West Coast Teams of the National Football League Correspond With Reduced Prevalence of Regular Season Injury.

    PubMed

    Brager, Allison J; Mistovich, Ronald J

    2017-02-01

    Brager, AJ and Mistovich, RJ. Game times and higher winning percentages of west coast teams of the National Football League correspond with reduced prevalence of regular season injury. J Strength Cond Res 31(2): 462-467, 2017-West coast teams of the National Football League are more statistically likely to win home night games against east coast opponents. The alignment of game times with daily rhythms of alertness is thought to contribute to this advantage. This study aims to determine whether rates of turnovers and injuries during the regular season, putative measures of mental and physical fatigue, impact winning percentages. Regular season schedules and rates of turnovers for each of the 32 teams were obtained from Pro-Football-Reference. We developed our own metric of injury risk for each position obtained from depth charts and regular season schedules. This metric compared cumulative weeks on injury reserve with cumulative time zone travel. West coast teams traveled 4 times as often as east coast teams. However, teams traveling eastward won twice as many games. There was no relationship between the extent and direction of travel and number of turnovers. Losing teams had more turnovers. The offensive and defensive lines in Central Time (CT) were placed on injury reserve 4 times as often as offensive and defensive lines in Pacific Time (PT). Injury prevalence in CT vs. PT was most prominent midseason. Plotting midseason game time relative to biological time revealed that PT teams play games closer to endogenous peaks in alertness, whereas CT teams play games closer to endogenous troughs in alertness. Overall, closer alignment of game time with the endogenous "alerting" signal may protect west coast teams from fatigue-related injuries and suggests for modified strength and conditioning programs.

  3. Post Earthquake Investigation Of The Mw7.8 Haida Gwaii, Canada, Rupture Area And Constraints On Earthquake Source Models

    NASA Astrophysics Data System (ADS)

    Haeussler, P. J.; Witter, R. C.; Wang, K.

    2013-12-01

    The October 28, 2012 Mw 7.8 Haida Gwaii, British Columbia, earthquake was the second largest historical earthquake recorded in Canada. Earthquake seismology and GPS geodesy shows this was an underthrusting event, in agreement with prior studies that indicated oblique underthrusting of the Haida Gwaii by the Pacific plate. Coseismic deformation is poorly constrained by geodesy, with only six GPS sites and two tide gauge stations anywhere near the rupture area. In order to better constrain the coseismic deformation, we measured the upper limit of sessile intertidal organisms at 26 sites relative to sea level. We dominantly measured the positions of bladder weed (fucus distichus - 617 observations) and the common acorn barnacle (Balanus balanoides - 686 observations). Physical conditions control the upper limit of sessile intertidal organisms, so we tried to find the quietest water conditions, with steep, but not overhanging faces, where slosh from wave motion was minimized. We focused on the western side of the islands as rupture models indicated that the greatest displacement was there. However, we were also looking for calm water sites in bays located as close as possible to the often tumultuous Pacific Ocean. In addition, we made 322 measurements of sea level that will be used to develop a precise tidal model and to evaluate the position of the organisms with respect to a common sea level datum. We anticipate the resolution of the method will be about 20-30 cm. The sites were focused on the western side of the Haida Gwaii from Wells Bay on the south up to Otard Bay to the north, with 5 transects across strike. We also collected data at the town of Masset, which lies outside of the deformation zone of the earthquake. We observed dried and desiccated bands of fucus and barnacles at two sites on the western coast of southern Moresby Island (Gowgia Bay and Wells Bay). Gowgia Bay had the strongest evidence of uplift with fucus that was dried out and apparently dead. A

  4. Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal.

    PubMed

    Silkworth, J B; Cutler, D S; Antrim, L; Houston, D; Tumasonis, C; Kaminsky, L S

    1989-07-01

    The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a

  5. Chronic Kidney Disease Is Characterized by “Double Trouble” Higher Pulse Pressure plus Night-Time Systolic Blood Pressure and More Severe Cardiac Damage

    PubMed Central

    Fedecostante, Massimiliano; Spannella, Francesco; Cola, Giovanna; Espinosa, Emma; Dessì-Fulgheri, Paolo; Sarzani, Riccardo

    2014-01-01

    Background Hypertension plays a key role in chronic kidney disease (CKD), but CKD itself affects the blood pressure (BP) profile. The aim of this study was to assess the association of BP profile with CKD and the presence of cardiac organ damage. Methods We studied 1805 patients, referred to our Hypertension Centre, in whom ABPM, blood tests, and echocardiography were clinically indicated. The glomerular filtration rate was estimated (eGFR) using the MDRD equation and CKD was defined as eGFR<60 mL/min/1.73 m2. Cardiac organ damage was evaluated by echocardiography. Results Among patients with CKD there were higher systolic blood pressure (SBP) during the night-time, greater prevalence of non-dippers (OR: 1.8) and increased pulse pressure (PP) during 24-hour period, daytime and night-time (all p<0.001). Patients with CKD had a greater LVM/h2.7 index, and a higher prevalence of left ventricular hypertrophy and diastolic dysfunction (all p<0.001). Nocturnal SBP and PP correlated more strongly with cardiac organ damage (p<0.001). Patients with CKD had a greater Treatment Intensity Score (p<0.001) in the absence of a significantly greater BP control. Conclusions CKD patients have an altered night-time pressure profile and higher PP that translate into a more severe cardiac organ damage. In spite of a greater intensity of treatment in most patients with CKD, BP control was similar to patients without CKD. Our findings indicate the need of a better antihypertensive therapy in CKD, better selected drugs, dosages and posology to provide optimal coverage of 24 hours and night-time BP. PMID:24465931

  6. Characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decreases in dexamethasone binding to rat hepatic cytosolic glucocorticoid receptor.

    PubMed

    Sunahara, G I; Lucier, G W; McCoy, Z; Bresnick, E H; Sanchez, E R; Nelson, K G

    1989-08-01

    An investigation of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the liver cytosolic glucocorticoid receptor (GRc) in intact and adrenalectomized (ADX) rats, using equilibrium binding analysis, sucrose gradient sedimentation, and affinity labeling experiments, clearly demonstrated that TCDD significantly reduced the binding capacity (Bmax) of the hepatic GRc but did not alter the apparent equilibrium dissociation constant (Kd). This effect was maximal after 24 hr and was still present 22 days after treatment. Western blot analysis revealed that TCDD treatment did not cause a comparable decrease in the levels of immunodetectable receptor protein, which suggests that the steroid-binding properties of the hepatic GRc are altered, rather than the absolute concentration of receptor protein. Studies of TCDD effects on the uptake of GRc by nuclei indicated that TCDD treatment did not alter the ability of the steroid-GRc complex to be taken up by nuclei; however, TCDD treatment did increase the total capacity of liver nuclei to bind steroid-GRc complexes. TCDD dose-response studies that compared the hepatic GRc steroid binding of ADX and intact rats indicated that adrenalectomy markedly enhanced the response to TCDD. Significant effects on the GRc binding in ADX animals were induced at TCDD doses that were 10,000 times lower than those required for a response in intact rats. Analysis of two other biochemical markers demonstrated that ADX rats were 10-fold more sensitive to the induction of microsomal benzo[a]pyrene hydroxylase but of similar sensitivity to reduction of epidermal growth factor receptor binding, when compared with the responses of intact animals. These data indicate that adrenal status may be important in modulating the responses of the animals to TCDD and that the alteration of the hepatic GRc pathway may have a role in some of the actions of TCDD.

  7. Selective catalytic hydrogenation of polynuclear heteroaromatic compounds using polymer-supported transition-metal compounds as catalyst. [5,6 and 7,8-benzoquinoline and quinoline

    SciTech Connect

    Fish, R.H.; Heinemann, H.

    1985-06-01

    This research program focused on the utilization of polymer-supported (polystyrene-divinylbenzene, PS-DVB) transition-metal catalysts in the selective catalytic hydrogenation of polynuclear heteroaromatic compounds that are known to be present in coal and coal liquids. We found that the polymer-supported chlorotris(triphenyl-phosphine)rhodium(1) was the most efficient catalyst for the regiospecific reduction of the nitrogen-containing ring in model-coal compounds such as quinoline, 5,6- and 7,8-benzoquinoline and acridine, and in one case, a heteroaromatic sulfur compound, benzothiophene. Interestingly, the polymer-supported rhodium catalyst was more active than the corresponding homogeneous analogue by relative rate factors of 10 to 20 depending on the substrate studied in the reduction. More importantly, a model coal liquid was found to have a relative rate of reduction of quinoline to 1,2,3,4-tetrahydroquinoline (THQ) that was 2.2 times faster than a similar experiment without the coal liquid constituents consisting of pyrene, tetralin, methylnaphthalene, p-cresol, quinoline, and 2-methylpyridine. Further experimentation clearly showed that the model coal liquid constituent, p-cresol, was responsible for the relative rate enhancement in the highly regiospecific reduction of quinoline to THQ. Nuclear magnetic resonance spectroscopy (NMR) experiments have given some insight into this rate-enhancement phenomena. We also found that 9,10-dihydrophenanthridine was an excellent catalytic transfer hydrogenation reagent in the presence of several homogeneous and polymer-supported transition-metal catalysts. Hydrogen was transferred to such acceptors as quinoline and acridine. We also evaluated dihydroquinoline as a donor solvent since THQ has been used as a donor solvent in coal liquefaction experiments. 48 refs., 4 figs., 2 tabs.

  8. Polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in tree swallows from the upper Hudson River, New York State, USA

    USGS Publications Warehouse

    Secord, Anne L.; McCarty, John P.; Echols, Kathy R.; Meadows, John C.; Gale, Robert W.; Tillitt, Donald E.

    1999-01-01

    The upper Hudson River of New York State, USA, is contaminated with polychlorinated biphenyls (PCBs) as a result of industrial discharges throughout the latter half of this century. In 1994 and 1995, we monitored the transfer of PCBs from aquatic sediments to a terrestrial wildlife community using the tree swallow (Tachycineta bicolor) as a model organism. Tree swallow eggs and nestlings were collected at four colonies established along a 40-km stretch of the upper Hudson River watershed. Samples were analyzed for total PCBs and PCB congeners, including non-ortho- and mono-ortho-substituted PCBs. Mean concentrations of PCBs in tree swallow eggs and nestlings ranged from 721 to 62,200 ng/g and were as much as 15 times greater than PCB concentrations in tree swallow eggs and nestlings collected from PCB-contaminated areas within the Great Lakes ecosystem. The corresponding 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) calculated using avian toxic equivalency factors ranged from 410 to 25,400 pg/g. Concentrations of PCB congener 77 (3,39,4,49-tetrachlorobiphenyl) were extremely elevated and were major contributors to the calculated TEQs. Homologue pattern comparisons between Hudson River and Saginaw River (Michigan, USA) ecosystems supported the hypothesis that a consistent Hudson River PCB source was the major contributor to PCBs in Hudson River tree swallows. The high concentrations of PCBs in Hudson River sediments and resultant concentrations observed in tree swallows were indicative of a potential elevated risk to these and other wildlife linked to the aquatic food web of the Hudson River ecosystem.

  9. 2,3,7,8-tetrachlorodibenzo-p-dioxin decrease expression of aryl hydrocarbon receptor in peripheral lymphocyte of β-thalassemia major patients

    PubMed Central

    Ghatrehsamani, Mahdi; Soleimani, Masoud; Esfahani, Behjat Al-Sadat Moayedi; Hakemi, Mazdak Ganjalikhani; Shirzad, Hedayatollah; Eskandari, Nahid; Adib, Minoo

    2015-01-01

    Background: β-thalassemia major is a hereditary disease with inefficient erythropoiesis. Level of inflammatory cytokine is elevated in these patients. In this study, we investigate the effect of aryl hydrocarbon receptor (AhR) ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on the expression of inflammatory mediators in β-thalassemia major patient's lymphocytes. Materials and Methods: Peripheral blood mononuclear cells of patients and healthy participants was isolated and cultured in favor of lymphocytes increment. Based on the treatment, we divided the cell into four groups. The orders of group's treatments were no treatment, tumor necrosis factor-α (TNF-α) treatment, TNF-α and TCDD treatment, TCDD treatment in Group 1–4, respectively. After cell culture, we extracted the cells RNA and converted them to cDNA. Real-time polymerase chain reaction was performed to assessment relative expression of caspase-1, NLRP3, and AhR. We compared all patient groups with equal healthy (control) groups. Results: Results showed that expression of caspase-1 in patients (Groups 1 and 2) was significantly lower than healthy individuals (P < 0.05). Although, no significant difference was found (Groups 1, 2, and control) in AhR gene expression (P > 0.05). Expression of AhR in other groups of patients (3 and 4) was significantly lower than control groups (P < 0.05). Expression of caspase-1 in Group 4 was significantly larger than the control group (P < 0.001). Conclusions: We show here that chronic inflammation decrease caspase-1 expression and exposure of human lymphocytes to TCDD promote caspase-1 expression. Furthermore, activation of AhR with TCDD decreases AhR expression in lymphocytes of β-thalassemia major disease. PMID:26605247

  10. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: Comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Bjeldanes, L.F.; Jinyoung Kim; Grose, K.R.; Bartholomew, J.C. ); Bradfield, C.A. )

    1991-11-01

    Indole-3-carbinol (I3C) is a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts. I3C is both an anti-initiator and a promoter of carcinogenesis. Consumption of I3C by humans and rodents can lead to marked increases in activities of cytochrome P-450-dependent monooxygenases and in a variety of phase II drug-metabolizing enzymes. The authors have reported previously that the enzyme-inducing activity of I3C is mediated through a mechanism requiring exposure of the compound to the low-pH environment of the stomach. They report here the aromatic hydrocarbon responsiveness-receptor K{sub d} values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields of the major acid condensation products of I3C. They also show that indolo (3,2-b)carbazole (ICZ) is produced form I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a K{sub d} of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC{sub 50} of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells. The binding affinity of ICZ is only a factor of 3.7 {times} 10{sup {minus}2} lower than that of the highly toxic environmental contaminant and cancer promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin. ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I3C.

  11. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced MUC5AC expression: aryl hydrocarbon receptor-independent/EGFR/ERK/p38-dependent SP1-based transcription.

    PubMed

    Lee, Yong C; Oslund, Karen L; Thai, Philip; Velichko, Sharlene; Fujisawa, Tomoyuki; Duong, Trang; Denison, Michael S; Wu, Reen

    2011-08-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxicant. Epidemiological studies have associated TCDD exposure with the development of chronic obstructive pulmonary disease, which is manifested by mucous/goblet cell hyperplasia. The purpose of this research was to elucidate the pathway/mechanisms that lead to TCDD-induced gene expression in both primary normal human bronchial epithelial cells and an immortalized cell line, HBE1, under air-liquid interface conditions. TCDD exposure induced a time-dependent elevation of MUC5AC mRNA and protein synthesis, and cytochrome p450 1A1 (CYP1A1) expression in these cells. Treatment with an aryl hydrocarbon receptor antagonist had no effect on TCDD-induced MUC5AC expression, but significantly suppressed CYP1A1 induction. However, treatments with inhibitors of signaling pathways and the expression of dominant negative mutants of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and p38, but not the inhibition of c-Jun N-terminal kinase pathway, abrogated MUC5AC induction, but not that of CYP1A1. These effects also occurred at the MUC5AC promoter-reporter level using the chimeric construct for a transient transfection study. Western blot analysis confirmed the phosphorylation of activated EGFR, ERK, and p38 signaling molecules, but not the c-Jun N-terminal kinase, in cells after TCDD exposure. Specificity protein 1 (Sp1) phosphorylation also occurred in cells after TCDD exposure. Both MUC5AC expression and the promoter activity were inhibited by mithramycin A, an inhibitor specific to Sp1-based transcription. These results lead to the conclusion that TCDD induced MUC5AC expression through a noncanonical aryl hydrocarbon receptor-independent, EGFR/ERK/p38-mediated signaling pathway-mediated/Sp1-based transcriptional mechanism.

  12. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters postnatal development of seminal vesicle epithelium.

    PubMed

    Hamm, J T; Sparrow, B R; Wolf, D; Birnbaum, L S

    2000-04-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to alter male reproductive development of laboratory animals through in utero and lactational exposure. As a result of exposure, the accessory glands of the male reproductive tract, including the seminal vesicle, are decreased in size as determined by total weight of the tissue. Analysis of seminal vesicle weights over time suggests that the changes may be transient. Administration of 1.0 microg/kg TCDD during gestation caused a significant decrease in seminal vesicle weights of offspring 8-11 months of age. We examined the effects of TCDD on seminal vesicles from rats exposed in utero and lactationally. Pregnant Long Evans rats were gavaged on gestation day 15 with 1.0 microg/kg TCDD in corn oil. Male pups were euthanized and necropsied on postnatal days (PND) 15, 25, 32, 49, 63, and 120. Seminal vesicles were weighed and then fixed in 10% neutral buffered formalin and processed for microscopic examination. Seminal vesicle weights were not significantly decreased until PND 32. Androgen receptor mRNA expression in PND 25 seminal vesicles was not different from control. In the present study, TCDD exposure decreased seminal vesicle epithelial branching and differentiation. Control epithelial cells had tall columnar morphology with relatively abundant cytoplasm, whereas TCDD-treated cells had rounded nuclei and less cytoplasm. In addition, immunolocalization of proliferating nuclear antigen was confined to undifferentiated basal epithelial cells of controls but was found in both basal and luminal cells of the treated seminal vesicle. Results indicate that the TCDD-induced impaired growth of the rat seminal vesicles is associated with a dramatic decrease in the development of the epithelium.

  13. Comparative toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to seven freshwater fish species during early life-stage development

    SciTech Connect

    Elonen, G.E.; Spehar, R.L.; Holcombe, G.W.; Johnson, R.D.; Fernandez, J.D.; Erickson, R.J.; Tietge, J.E.; Cook, P.M.

    1998-03-01

    The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to fathead minnow (Pimephales promelas), channel catfish (Ictalurus punctatus), lake herring (Coregonus artedii), medaka (Oryzias latipes), white sucker (Catastomus commersoni), northern pike (Esox lucius), and zebrafish (Danio danio) were observed during early life-stage development after waterborne exposure of fertilized eggs. Species sensitivity based on TCDD-C{sub egg} (TCDD concentration in eggs) was determined by effects observed over a 32-d period for all species except lake herring in which a 100-d period was used. Signs of TCDD toxicity, including edema, hemorrhaging, and craniofacial malformations were essentially identical to those observed in salmonids following TCDD egg exposure and preceded or accompanied mortality most often during the period from hatch through swim-up. The no-observed-effect concentrations and lowest-observed-effect concentrations, based on significant decreases in survival and growth as compared to the controls, ranged from 175 and 270 pg/g for lake herring to 424 and 2,000 pg/g for zebrafish, respectively. Shapes of concentration-response curves, expressed as TCDD-C{sub egg} versus percent mortality, were similar for all species and were consistently steep suggesting that the mechanism of action of TCDD is the same among these species. The LC{sub egg}50s ranged from 539 pg/g for the fathead minnow to 2,610 pg/g for zebrafish. Comparisons of LC{sub egg}50s indicate that the tested species were approximately 8 to 38 times less sensitive to TCDD than lake trout, the most sensitive species evaluated to date. When LC{sub egg}50s are normalized to the fraction lipid in eggs (LC{sub egg,f}50s), the risk to early life stage survival for the species tested ranges from 16- to 180-fold less than for lake trout.

  14. 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Differentially Suppresses Angiogenic Responses in Human Placental Vein and Artery Endothelial Cells

    PubMed Central

    Li, Yan; Wang, Kai; Zou, Qing-Yun; Magness, Ronald R.; Zheng, Jing

    2015-01-01

    Placental angiogenesis is dramatically increased during pregnancy in association with the elevated placental blood flows to support the rapidly growing fetus. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant and a ligand of aryl hydrocarbon receptor (AhR). Herein, we investigated the effects of TCDD on proliferation, migration, and viability of fetoplacental endothelial cells in response to a complete growth medium which contained serum and growth supplement using human umbilical cord vein (HUVECs) and artery (HUAECs) cells as models. We found that TCDD dose- and time-dependently inhibited (p < 0.05) proliferation of HUVECs and HUAECs. Treatment with TCDD at 10 nM for 6 days inhibited (p < 0.05) migration (by ~30%) of HUAECs, but not HUVECs. TCDD at 10 nM also attenuated (p < 0.05) viability of HUVECs and HUAECs. Interestingly, specific AhR siRNA blocked (p < 0.05) the TCDD-inhibited cellular responses in HUAECs, but not HUVECs. Nonetheless, TCDD at 10 nM neither affected the cell cycle process, nor did it induce cell apoptosis in HUVECs and HUAECs. In addition, TCDD at 10 nM also did not alter activation of ERK1/2 and AKT1 in HUVECs and HUAECs. Collectively, TCDD suppresses proliferation and/or migration (two key steps of angiogenesis) of HUVECs and HUAECs independent and dependent of AhR, respectively. These data suggest that TCDD inhibited growth of HUVECs and HUAECs via decreasing cell viability. Thus, TCDD may inhibit fetoplacental angiogenesis, leading to negative pregnancy outcomes. PMID:26275813

  15. Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Shan, Qiuli; Wang, Jing; Huang, Fengchen; Lv, Xiaowen; Ma, Min; Du, Yuguo

    2014-04-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE{sup −/−} mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE{sup −/−} mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE{sup −/−} mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs.

  16. Attenuation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by resveratrol: a comparative study with different routes of administration.

    PubMed

    Ishida, Takumi; Takeda, Tomoki; Koga, Takayuki; Yahata, Masahiro; Ike, Ayako; Kuramoto, Chihiro; Taketoh, Junko; Hashiguchi, Isamu; Akamine, Akifumi; Ishii, Yuji; Yamada, Hideyuki

    2009-05-01

    The activation of aryl hydrocarbon receptor with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to be antagonized by co-treatment with resveratrol. However, such a protective effect has been suggested from studies using subcutaneous injection of this polyphenol. To evaluate the practical usefulness of resveratrol, this study examined the protective effect of oral resveratrol on the sub-acute toxic effects of TCDD in C57BL/6J mice. A TCDD-induced wasting syndrome was not alleviated by treating mice for 28 d with oral resveratrol. However, subcutaneous injection of resveratrol for 5 d significantly improved the symptoms. Neither oral nor subcutaneous administration of resveratrol alleviated TCDD-induced hepatomegaly and thymic atrophy. Steatosis produced by TCDD was markedly counteracted by co-treatment with oral resveratrol, whereas resveratrol injected subcutaneously had no effect. The reason for the lack of protective effect via the latter dosing route was assumed to be due to the minor accumulation of hepatic lipids 5 d after TCDD treatment. To clarify the mechanisms, the activity of ethoxyresorufin O-deethylase and the content of thiobarbituric acid-reactive substances in the liver were measured. Both indices increased by TCDD treatment were significantly suppressed by subcutaneous injection of resveratrol. In contrast, oral resveratrol failed to rescue them. In agreement with the greater protective effects of subcutaneously-injected resveratrol, pharmacokinetic studies indicated that the area under the curve extrapolated to infinity (AUC(infinity)) was 8.2-times greater following subcutaneous injection compared with oral administration. These data suggest that 1) oral resveratrol is attractive candidate as an agent capable of combating dioxin toxicity and 2) increasing the bioavailability of this polyphenol enhances its protective effect.

  17. Interactive effects of n-TiO2 and 2,3,7,8-TCDD on the marine bivalve Mytilus galloprovincialis.

    PubMed

    Canesi, Laura; Frenzilli, Giada; Balbi, Teresa; Bernardeschi, Margherita; Ciacci, Caterina; Corsolini, Simonetta; Della Torre, Camilla; Fabbri, Rita; Faleri, Claudia; Focardi, Silvano; Guidi, Patrizia; Kočan, Anton; Marcomini, Antonio; Mariottini, Michela; Nigro, Marco; Pozo-Gallardo, Karla; Rocco, Lucia; Scarcelli, Vittoria; Smerilli, Arianna; Corsi, Ilaria

    2014-08-01

    Despite the growing concern over the potential biological impact of nanoparticles (NPs) in the aquatic environment, little is known about their interactions with other pollutants. The bivalve Mytilus sp, largely utilized as a sentinel for marine contamination, has been shown to represent a significant target for different types of NP, including n-TiO2, one of the most widespread in use. In this work, the possible interactive effects of n-TiO2 and 2,3,7,8-TCDD, chosen as models of NP and organic contaminant, respectively, were investigated in Mytilus galloprovincialis. In vitro experiments with n-TiO2 and TCDD, alone and in combination, were carried out in different conditions (concentrations and times of exposure), depending on the target (hemocytes, gill cells and biopsies) and the endpoint measured. Mussels were also exposed in vivo to n-TiO2 (100 μg L(-1)) or to TCDD (0.25 μg L(-1)), alone and in combination, for 96 h. A wide range of biomarkers, from molecular to tissue level, were measured: lysosomal membrane stability and phagocytosis in hemocytes, ATP-binding cassette efflux transporters in gills (gene transcription and efflux activity), several biomarkers of genotoxicity in gill and digestive cells (DNA damage, random amplified polymorphic DNA-RAPD changes), lysosomal biomarkers and transcription of selected genes in the digestive gland. The results demonstrate that n-TiO2 and TCDD can exert synergistic or antagonistic effects, depending on experimental condition, cell/tissue and type of measured response. Some of these interactions may result from a significant increase in TCDD accumulation in whole mussel organisms in the presence of n-TiO2, indicating a Trojan horse effect. The results represent the most extensive data obtained so far on the sub-lethal effects of NPs and organic contaminants in aquatic organisms. Moreover, these data extend the knowledge on the molecular and cellular targets of NPs in bivalves.

  18. Polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents in tree swallows from the upper Hudson River, New York State, USA

    USGS Publications Warehouse

    Secord, A.L.; McCarty, J.P.; Echols, K.R.; Meadows, J.C.; Gale, R.W.; Tillitt, D.E.

    1999-01-01

    The upper Hudson River of New York State, USA, is contaminated with polychlorinated biphenyls (PCBs) as a result of industrial discharges throughout the latter half of this century. In 1994 and 1995, we monitored the transfer of PCBs from aquatic sediments to a terrestrial wildlife community using the tree swallow (Tachycineta bicolor) as a model organism. Tree swallow eggs and nestlings were collected at four colonies established along a 40-km stretch of the upper Hudson River watershed. Samples were analyzed for total PCBs and PCB congeners, including non-ortho- and mono- ortho-substituted PCBs. Mean concentrations of PCBs in tree swallow eggs and nestlings ranged from 721 to 62,200 ng/g and were as much as 15 times greater than PCB concentrations in tree swallow eggs and nestlings collected from PCB-contaminated areas within the Great Lakes ecosystem. The corresponding 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) calculated using avian toxic equivalency factors ranged from 410 to 25,400 pg/g. Concentrations of PCB congener 77 (3,3',4,4'-tetrachlorobiphenyl) were extremely elevated and were major contributors to the calculated TEQs. Homologue pattern comparisons between Hudson River and Saginaw River (Michigan, USA) ecosystems supported the hypothesis that a consistent Hudson River PCB source was the major contributor to PCBs in Hudson River tree swallows. The high concentrations of PCBs in Hudson River sediments and resultant concentrations observed in tree swallows were indicative of a potential elevated risk to these and other wildlife linked to the aquatic food web of the Hudson River ecosystem.

  19. Younger age at initiation of the human papillomavirus (HPV) vaccination series is associated with higher rates of on-time completion.

    PubMed

    St Sauver, Jennifer L; Rutten, Lila J Finney; Ebbert, Jon O; Jacobson, Debra J; McGree, Michaela E; Jacobson, Robert M

    2016-08-01

    Vaccination rates for human papillomavirus (HPV) have remained disappointingly low. It is critical to identify methods to increase on-time vaccine series completion rates (before 13 or 15years). To determine whether younger age (9 to 10years of age) at HPV vaccine series initiation was associated with improved on-time completion rates compared to initiation at 11 to 12years, we examined the prevalence of on-time HPV vaccine series completion rates from August 2006 through December 2012 in a large, population-based cohort of children and adolescents (aged 9.5 to 27years) residing in Olmsted County, MN on December 31, 2012 (n=36,223). We compared age at vaccine initiation between individuals who successfully completed both 2 and 3 doses of the vaccination series on-time (before age 13.5 or 15.0years) using multivariate logistic regression. On-time completion of both 2 and 3 doses of the vaccine series by age 13.5 or 15.0years was significantly associated with initiation at 9 to 10years as compared to 11 to 12years after adjusting for sex, race, insurance status, frequent health care visits, and year of first vaccination (all p<.01). Interventions focused on beginning the vaccination series at 9 to 10years of age may result in higher rates of timely series completion.

  20. Dynamics of higher-order rational solitons for the nonlocal nonlinear Schrödinger equation with the self-induced parity-time-symmetric potential.

    PubMed

    Wen, Xiao-Yong; Yan, Zhenya; Yang, Yunqing

    2016-06-01

    The integrable nonlocal nonlinear Schrödinger equation with the self-induced parity-time-symmetric potential [M. J. Ablowitz and Z. H. Musslimani, Phys. Rev. Lett. 110, 064105 (2013)] is investigated, which is an integrable extension of the standard nonlinear Schrödinger equation. Its novel higher-order rational solitons are found using the nonlocal version of the generalized perturbation (1,N-1)-fold Darboux transformation. These rational solitons illustrate abundant wave structures for the distinct choices of parameters (e.g., the strong and weak interactions of bright and dark rational solitons). Moreover, we also explore the dynamical behaviors of these higher-order rational solitons with some small noises on the basis of numerical simulations.