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Sample records for 5-6 times higher

  1. Stroke in ancient times: a reinterpretation of Psalms 137:5,6.

    PubMed

    Resende, Luiz Antonio de Lima; Weber, Silke Anna Theresa; Bertotti, Marcelo Fernando Zeugner; Agapejev, Svetlana

    2008-09-01

    Stroke was probably first described in Psalms 136: 5-6 of the Catholic Bible, and Psalms 137:5-6 of the Evangelical Bible. Based on the Portuguese, Spanish, English, German, Dutch, Russian, Greek, and original Hebrew Bible, the significance of this Psalm is the invocation of a punishment, of which the final result would be a stroke of the left middle cerebral artery, causing motor aphasia and right hemiparesis.

  2. 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…

  3. Mechanistic analysis for time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone levels in 5/6 nephrectomized rats

    PubMed Central

    Wu-Wong, J Ruth; Nakane, Masaki; Chen, Yung-wu; Mizobuchi, Masahide

    2013-01-01

    This study investigates the time-dependent effects of cinacalcet on serum calcium, phosphorus, and parathyroid hormone (PTH) levels in 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency. In this study, 5/6 NX male, Sprague–Dawley rats were treated with vehicle or cinacalcet (10 mg/kg, oral, 1× daily). On Day 0 (before treatment), Day 12 and 13 after treatment (to approximate the clinical practice), and also at 0, 1, 4, 8, 16, and 24 hours after the last dosing, blood was collected for analysis. After 12 or 13 days of cinacalcet treatment, modest changes were observed in serum Ca and phosphorus (Pi), while PTH decreased by >45% to Sham levels (152 ± 15 pg/mL). Detailed mapping found that cinacalcet caused a significant time-dependent decrease in serum Ca following dosing, reaching a lowest point at 8 hours (decrease by 20% to 8.43 ± 0.37 mg/dL), and then returning to normal at 24 hours. Cinacalcet also caused a significant increase in serum Pi levels (by 18%). To investigate the potential mechanism of action, a broad approach was taken by testing cinacalcet in a panel of 77 protein-binding assays. Cinacalcet interacted with several channels, transporters, and neurotransmitter receptors, some of which are involved in brain and heart, and may impact Ca homeostasis. Cinacalcet dose-dependently increased brain natriuretic peptide (BNP) mRNA expression by 48% in cardiomyocytes, but had no significant effects on left ventricular hypertrophy and cardiac function. The results suggest that cinacalcet's hypocalcemic effect may be due to its nonspecific interaction with other receptors in brain and heart. PMID:24303131

  4. 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;…

  5. Crystal structure of 5,6-bis(9H-carbazol-9-yl)benzo[c][1,2,5]thiadiazole: distortion from a hypothetical higher-symmetry structure.

    PubMed

    Averkiev, Boris B; Davydenko, Iryna; Wang, Xu; Barlow, Stephen; Marder, Seth R

    2017-04-01

    Nucleophilic substitution of F atoms in 5,6-difluorobenzo[c][1,2,5]thiadiazole (DFBT) for carbazole could be potentially interesting as a novel way of synthesizing building blocks for new conjugated materials for applications in organic chemistry. The crystal structures of 5,6-bis(9H-carbazol-9-yl)benzo[c][1,2,5]thiadiazole (DCBT), C30H18N4S, and its hydrate, C30H18N4S·0.125H2O, were investigated using single-crystal X-ray analysis. The hydrate contains two symmetry-independent DCBT molecules. The dihedral angles between the plane of the central benzothiadiazole fragment and that of the carbazole units vary between 50.8 and 69.9°, indicating conformational flexibility of the DCBT molecule in the crystals, which is consistent with quantum chemical calculations. The analysis of the crystal packing of DCBT revealed that the experimental triclinic structure could be described as a distortion from a hypothetical higher-symmetry monoclinic structure. The quantum chemical calculations of two possible monoclinic structures, which are related to the experimental structure by a shifting of molecular layers, showed that the proposed structures are higher in energy by 5.4 and 10.1 kcal mol(-1). This energy increase is caused by less dense crystal packings of the symmetric structures, which results in a decrease of the number of intermolecular interactions.

  6. 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…

  7. 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

  8. 44 CFR 5.6 - Congressional information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Congressional information. 5.6 Section 5.6 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION General Provisions § 5.6...

  9. 1 CFR 5.6 - Daily publication.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day....

  10. 1 CFR 5.6 - Daily publication.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day....

  11. 1 CFR 5.6 - Daily publication.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day....

  12. 1 CFR 5.6 - Daily publication.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day....

  13. 1 CFR 5.6 - Daily publication.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Daily publication. 5.6 Section 5.6 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER GENERAL § 5.6 Daily publication. There shall be an edition of the Federal Register published for each official Federal working day....

  14. 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…

  15. 43 CFR 1610.5-6 - Revision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Revision. 1610.5-6 Section 1610.5-6 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource...

  16. 36 CFR 5.6 - Commercial vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Commercial vehicles. 5.6 Section 5.6 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR... other vehicles when used in transporting movable property for a fee or profit, either as a direct...

  17. 36 CFR 5.6 - Commercial vehicles.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Commercial vehicles. 5.6 Section 5.6 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR... other vehicles when used in transporting movable property for a fee or profit, either as a direct...

  18. 36 CFR 5.6 - Commercial vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Commercial vehicles. 5.6 Section 5.6 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR... other vehicles when used in transporting movable property for a fee or profit, either as a direct...

  19. 36 CFR 5.6 - Commercial vehicles.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Commercial vehicles. 5.6... COMMERCIAL AND PRIVATE OPERATIONS § 5.6 Commercial vehicles. (a) The term “Commercial vehicle” as used in... other vehicles when used in transporting movable property for a fee or profit, either as a direct...

  20. 36 CFR 5.6 - Commercial vehicles.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Commercial vehicles. 5.6... COMMERCIAL AND PRIVATE OPERATIONS § 5.6 Commercial vehicles. (a) The term “Commercial vehicle” as used in... other vehicles when used in transporting movable property for a fee or profit, either as a direct...

  1. 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…

  2. 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…

  3. 29 CFR 5.6 - Enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... WORK HOURS AND SAFETY STANDARDS ACT) Davis-Bacon and Related Acts Provisions and Procedures § 5.6...-Bacon Act, that the contractor has disregarded its obligations to employees and subcontractors),...

  4. 29 CFR 5.6 - Enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... WORK HOURS AND SAFETY STANDARDS ACT) Davis-Bacon and Related Acts Provisions and Procedures § 5.6...-Bacon Act, that the contractor has disregarded its obligations to employees and subcontractors),...

  5. 29 CFR 5.6 - Enforcement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... WORK HOURS AND SAFETY STANDARDS ACT) Davis-Bacon and Related Acts Provisions and Procedures § 5.6...-Bacon Act, that the contractor has disregarded its obligations to employees and subcontractors),...

  6. 29 CFR 5.6 - Enforcement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... WORK HOURS AND SAFETY STANDARDS ACT) Davis-Bacon and Related Acts Provisions and Procedures § 5.6...-Bacon Act, that the contractor has disregarded its obligations to employees and subcontractors),...

  7. 29 CFR 5.6 - Enforcement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... WORK HOURS AND SAFETY STANDARDS ACT) Davis-Bacon and Related Acts Provisions and Procedures § 5.6...-Bacon Act, that the contractor has disregarded its obligations to employees and subcontractors),...

  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. 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…

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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…

  8. 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.

  9. 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…

  10. 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…

  11. 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,"…

  12. 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…

  13. 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…

  14. 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…

  15. 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)

  16. 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.…

  17. 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…

  18. 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…

  19. 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…

  20. Smc5/6 complex regulates Sgs1 recombination functions.

    PubMed

    Bermúdez-López, Marcelino; Aragon, Luis

    2016-09-23

    The family of RecQ helicases is evolutionary conserved from bacteria to humans and play key roles in genome stability. The budding yeast RecQ helicase Sgs1 has been implicated in several key processes during the repair of DNA damage by homologous recombination as part of the STR complex (Sgs1-Top3-Rmi1). Limited information on how is Sgs1 recruited and regulated at sites of damage is available. Recently, we and others have uncover a direct link between the Smc5/6 complex and Sgs1. Most roles of Sgs1 during recombination, including DNA end resection, Holiday junction dissolution, and crossover suppression, are regulated through Mms21-dependent SUMOylation. Smc5/6 first acts as a recruiting platform for STR and then SUMOylates STR components to regulate their function. Importantly, the assembly of STR is totally independent of Smc5/6. Here, we provide a brief overview of STR regulation by Smc5/6.

  1. 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.

  2. 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.

  3. 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.

  4. 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…

  5. 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…

  6. 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 ...

  7. 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

  8. 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,…

  9. 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…

  10. 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…

  11. Diastereoselective synthesis of 2,3,4,5,6-pentafluoroheptanes.

    PubMed

    Farran, Daniel; Slawin, Alexandra M Z; Kirsch, Peer; O'Hagan, David

    2009-09-18

    A stereocontrolled synthesis of alkanes containing five contiguous fluorine atoms is presented. The compounds were prepared by sequential fluorination of diastereoisomeric alcohol-diepoxides. The chemistry involved epoxide ring-opening with HF.NEt(3) and deshydroxyfluorination reactions of free alcohols with Deoxo-Fluor. The fluorination reactions were all highly stereospecific, with all five fluorines being incorporated in three sequential steps. Three different diastereoisomers of the 2,3,4,5,6-pentafluoroheptyl motif were prepared as heptane-1,7-diol derivatives, a structural format amenable for incorporation of the vicinal pentafluoro scaffold into larger molecular architectures.

  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. 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.

  14. Early development of Drosophila embryos requires Smc5/6 function during oogenesis.

    PubMed

    Tran, Martin; Tsarouhas, Vasilios; Kegel, Andreas

    2016-07-15

    Mutations in structural maintenance of chromosomes (Smc) proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis.

  15. Specialized interfaces of Smc5/6 control hinge stability and DNA association

    PubMed Central

    Alt, Aaron; Dang, Hung Q.; Wells, Owen S.; Polo, Luis M.; Smith, Matt A.; McGregor, Grant A.; Welte, Thomas; Lehmann, Alan R.; Pearl, Laurence H.; Murray, Johanne M.; Oliver, Antony W.

    2017-01-01

    The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure—which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual ‘molecular latch' and a functional ‘hub'. Defined mutations in these interfaces cause severe phenotypic effects with sensitivity to DNA-damaging agents in fission yeast and reduced viability in human cells. We show that the Smc5/6-hinge complex binds preferentially to ssDNA and that this interaction is affected by both ‘latch' and ‘hub' mutations, suggesting a key role for these unique features in controlling DNA association by the Smc5/6 complex. PMID:28134253

  16. Early development of Drosophila embryos requires Smc5/6 function during oogenesis

    PubMed Central

    Tran, Martin; Tsarouhas, Vasilios

    2016-01-01

    ABSTRACT Mutations in structural maintenance of chromosomes (Smc) proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis. PMID:27288507

  17. 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.

  18. 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.

  19. 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…

  20. "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…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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.

  6. 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.

  7. Smc5/6 Coordinates Formation and Resolution of Joint Molecules with Chromosome Morphology to Ensure Meiotic Divisions

    PubMed Central

    Blitzblau, Hannah G.; Newcombe, Sonya; Chan, Andrew Chi-ho; Newnham, Louise; Li, Zhaobo; Gray, Stephen; Herbert, Alex D.; Arumugam, Prakash; Hochwagen, Andreas; Hunter, Neil; Hoffmann, Eva

    2013-01-01

    During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe. PMID:24385939

  8. Photophysics of poly(2,3,4,5,6-pentafluoro styrene) film

    NASA Technical Reports Server (NTRS)

    O'Connor, Donald B.; Scott, Gary W.; Coulter, Daniel R.; Miskowski, Vincent M.; Yavrouian, Andre

    1990-01-01

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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 18 CFR 5.6 - Pre-application document.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a plan and schedule for all pre-application activity that incorporates the time frames for pre..., powerhouses, tailraces, and other structures proposed to be included as part of the project or connected... sea level), gross storage capacity of any impoundments; (C) The number, type, and minimum and...

  16. 18 CFR 5.6 - Pre-application document.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... a plan and schedule for all pre-application activity that incorporates the time frames for pre..., powerhouses, tailraces, and other structures proposed to be included as part of the project or connected... sea level), gross storage capacity of any impoundments; (C) The number, type, and minimum and...

  17. Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA

    PubMed Central

    Zabrady, Katerina; Adamus, Marek; Vondrova, Lucie; Liao, Chunyan; Skoupilova, Hana; Novakova, Marketa; Jurcisinova, Lenka; Alt, Aaron; Oliver, Antony W.; Lehmann, Alan R.; Palecek, Jan J.

    2016-01-01

    SMC5/6 is a highly conserved protein complex related to cohesin and condensin, which are the key components of higher-order chromatin structures. The SMC5/6 complex is essential for proliferation in yeast and is involved in replication fork stability and processing. However, the precise mechanism of action of SMC5/6 is not known. Here we present evidence that the NSE1/NSE3/NSE4 sub-complex of SMC5/6 binds to double-stranded DNA without any preference for DNA-replication/recombination intermediates. Mutations of key basic residues within the NSE1/NSE3/NSE4 DNA-binding surface reduce binding to DNA in vitro. Their introduction into the Schizosaccharomyces pombe genome results in cell death or hypersensitivity to DNA damaging agents. Chromatin immunoprecipitation analysis of the hypomorphic nse3 DNA-binding mutant shows a reduced association of fission yeast SMC5/6 with chromatin. Based on our results, we propose a model for loading of the SMC5/6 complex onto the chromatin. PMID:26446992

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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;…

  4. 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…

  5. 7 CFR 5.6 - Revision of the parity price of a commodity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Revision of the parity price of a commodity. 5.6 Section 5.6 Agriculture Office of the Secretary of Agriculture DETERMINATION OF PARITY PRICES § 5.6 Revision of the parity price of a commodity. (a) Initiation of hearings. The “modernized” parity...

  6. 7 CFR 5.6 - Revision of the parity price of a commodity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Revision of the parity price of a commodity. 5.6 Section 5.6 Agriculture Office of the Secretary of Agriculture DETERMINATION OF PARITY PRICES § 5.6 Revision of the parity price of a commodity. (a) Initiation of hearings. The “modernized” parity...

  7. 7 CFR 5.6 - Revision of the parity price of a commodity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Revision of the parity price of a commodity. 5.6 Section 5.6 Agriculture Office of the Secretary of Agriculture DETERMINATION OF PARITY PRICES § 5.6 Revision of the parity price of a commodity. (a) Initiation of hearings. The “modernized” parity...

  8. 7 CFR 5.6 - Revision of the parity price of a commodity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Revision of the parity price of a commodity. 5.6 Section 5.6 Agriculture Office of the Secretary of Agriculture DETERMINATION OF PARITY PRICES § 5.6 Revision of the parity price of a commodity. (a) Initiation of hearings. The “modernized” parity...

  9. 7 CFR 5.6 - Revision of the parity price of a commodity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Revision of the parity price of a commodity. 5.6 Section 5.6 Agriculture Office of the Secretary of Agriculture DETERMINATION OF PARITY PRICES § 5.6 Revision of the parity price of a commodity. (a) Initiation of hearings. The “modernized” parity...

  10. ALMA Reveals Weak [N ii] Emission in "Typical" Galaxies and Intense Starbursts at z = 5-6

    NASA Astrophysics Data System (ADS)

    Pavesi, Riccardo; Riechers, Dominik A.; Capak, Peter L.; Carilli, Christopher L.; Sharon, Chelsea E.; Stacey, Gordon J.; Karim, Alexander; Scoville, Nicholas Z.; Smolčić, Vernesa

    2016-12-01

    We report interferometric measurements of [N ii] 205 μm fine-structure line emission from a representative sample of three galaxies at z = 5-6 using the Atacama Large (sub)Millimeter Array (ALMA). These galaxies were previously detected in [C ii] and far-infrared continuum emission and span almost two orders of magnitude in star formation rate (SFR). Our results show at least two different regimes of ionized interstellar medium properties for galaxies in the first billion years of cosmic time, separated by their {L}[{{C}{{II}}]}/{L}[{{N}{{II}}]} ratio. We find extremely low [N ii] emission compared to [C ii] ({L}[{{C}{{II}}]}/{L}[{{N}{{II}}]}={68}-28+200) from a “typical” ˜ {L}{UV}* star-forming galaxy, likely directly or indirectly (by its effect on the radiation field) related to low dust abundance and low metallicity. The infrared-luminous modestly star-forming Lyman-break galaxy (LBG) in our sample is characterized by an ionized-gas fraction ({L}[{{C}{{II}}]}/{L}[{{N}{{II}}]}≲ 20) typical of local star-forming galaxies and shows evidence for spatial variations in its ionized-gas fraction across an extended gas reservoir. The extreme SFR, warm and compact dusty starburst AzTEC-3 shows an ionized fraction higher than expected given its SFR surface density ({L}[{{C}{{II}}]}/{L}[{{N}{{II}}]}=22+/- 8) suggesting that [N ii] dominantly traces a diffuse ionized medium rather than star-forming H ii regions in this type of galaxy. This highest redshift sample of [N ii] detections provides some of the first constraints on ionized and neutral gas modeling attempts and on the structure of the interstellar medium at z = 5-6 in “normal” galaxies and starbursts.

  11. Microwave-Assisted Synthesis of 2-Aryl-2-oxazolines, 5,6-Dihydro-4H-1,3-oxazines, and 4,5,6,7-Tetrahydro-1,3-oxazepines.

    PubMed

    Mollo, María C; Orelli, Liliana R

    2016-12-02

    The first general procedure for the synthesis of 5- to 7-membered cyclic iminoethers by microwave-assisted cyclization of ω-amido alcohols promoted by polyphosphoric acid (PPA) esters is presented. 2-Aryl-2-oxazolines and 5,6-dihydro-4H-1,3-oxazines were efficiently prepared using ethyl polyphosphate/CHCl3. Trimethylsilyl polyphosphate in solvent-free conditions allowed for the synthesis of hitherto-unreported 4,5,6,7-tetrahydro-1,3-oxazepines. The method involves good to excellent yields and short reaction times.The reaction mechanism and the role of PPA esters were investigated in a chiral substrate.

  12. 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…

  13. 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…

  14. Thermal responses to 5. 6-GHz radiofrequency radiation in anesthetized rats: effect of chlorpromazine

    SciTech Connect

    Jauchem, J.R.; Frei, M.R.; Heinmets, F.

    1988-01-01

    Anesthetized rats were exposed to 5.6-GHz continuous wave radiofrequency radiation at an average power density of 60 mW/cm2 (average specific absorption rate 12 W/kg). Exposure was performed to raise colonic temperature from 38.5 to 39.5 degrees C. Following acute administration of chlorpromazine, body temperature exhibited a faster return to baseline temperature when exposure was discontinued. When exposure was initiated at 38.5 degrees C and continued until lethal temperatures resulted, chlorpromazine-treated animals exhibited significantly shorter survival times than saline-treated animals. Thus, although chlorpromazine enhanced thermo-regulatory efficiency at colonic temperatures below 39.5 degrees C, the drug caused increased susceptibility to terminal radiofrequency radiation exposure. The present results, when compared to previous studies of irradiation at 2.8 GHz, indicate that the effects of chlorpromazine on thermal responses to RFR during intermittent and terminal exposure are similar at both 2.8 and 5.6 GHz.

  15. Thermal responses to 5. 6-GHz radiofrequency radiation in anesthetized rats. Effect of chlorpromazine

    SciTech Connect

    Jauchem, J.R.; Frei, M.R.; Heinmets, F.

    1988-01-01

    Anesthetized rats were exposed to 5.6-GHz continuous-wave radiofrequency radiation (RFR) at an average power density of 60 mW/Sq. cm (average specific absorption rate 12 W/kg). Exposure was performed to raise colonic temperature from 38.5 to 39.5C. Following acute administration of chlorpromazine, body temperature exhibited a faster return to baseline temperature when exposure was discontinued. When exposure was initiated at 38.5C and continued until lethal temperature resulted, chlorpromazine-treated animals exhibited significantly shorter survival times than saline-treated animals. Thus, although chlorpromazine enhanced thermoregulatory efficiency at colonic temperature below 39.5 deg C, the drug caused increased susceptibility to terminal RFR. The present results, when compared with previous studies of irradiation at 2.8 GHz, indicate that the effects of chlorpromazine on thermal response to RFR during intermittent and terminal exposure are similar at both 2.8 and 5.6 GHz.

  16. 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…

  17. 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 ...

  18. 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…

  19. Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles[S

    PubMed Central

    Paillasse, Michael R.; Saffon, Nathalie; Gornitzka, Heinz; Silvente-Poirot, Sandrine; Poirot, Marc; de Medina, Philippe

    2012-01-01

    We recently established that drugs used for the treatment and the prophylaxis of breast cancers, such as tamoxifen, were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of 5,6α-epoxy-cholesterol (5,6α-EC) and 5,6β-epoxy-cholesterol (5,6β-EC). This could be considered a paradox because epoxides are known as alkylating agents with putative carcinogenic properties. We report here that, as opposed to the carcinogen styrene-oxide, neither of the ECs reacted spontaneously with nucleophiles. Under catalytic conditions, 5,6β-EC remains unreactive whereas 5,6α-EC gives cholestan-3β,5α-diol-6β-substituted compounds. These data showed that 5,6-ECs are stable epoxides and unreactive toward nucleophiles in the absence of a catalyst, which contrasts with the well-known reactivity of aromatic and aliphatic epoxides. These data rule out 5,6-EC acting as spontaneous alkylating agents. In addition, these data support the existence of a stereoselective metabolism of 5,6α-EC. PMID:22285872

  20. Cholesterol-5,6-epoxides: chemistry, biochemistry, metabolic fate and cancer.

    PubMed

    Poirot, Marc; Silvente-Poirot, Sandrine

    2013-03-01

    In the nineteen sixties it was proposed that cholesterol might be involved in the etiology of cancers and cholesterol oxidation products were suspected of being causative agents. Researchers had focused their attention on cholesterol-5,6-epoxides (5,6-ECs) based on several lines of evidence: 1) 5,6-ECs contained an oxirane group that was supposed to confer alkylating properties such as those observed for aliphatic and aromatic epoxides. 2) cholesterol-5,6-epoxide hydrolase (ChEH) was induced in pre-neoplastic lesions of skin from rats exposed to ultraviolet irradiations and ChEH was proposed to be involved in detoxification processes like other epoxide hydrolases. However, 5,6-ECs failed to induce carcinogenicity in rodents which ruled out a potent carcinogenic potential for 5,6-ECs. Meanwhile, clinical studies revealed an anomalous increase in the concentrations of 5,6β-EC in the nipple fluids of patients with pre-neoplastic breast lesions and in the blood of patients with endometrious cancers, suggesting that 5,6-ECs metabolism could be linked with cancer. Paradoxically, ChEH has been recently shown to be totally inhibited by therapeutic concentrations of tamoxifen (Tam), which is one of the main drugs used in the hormonotherapy and the chemoprevention of breast cancers. These data would suggest that the accumulation of 5,6-ECs could represent a risk factor, but we found that 5,6-ECs were involved in the induction of breast cancer cell differentiation and death induced by Tam suggesting a positive role of 5,6-ECs. These observations meant that the biochemistry and the metabolism of 5,6-ECs needed to be extensively studied. We will review the current knowledge and the future direction of 5,6-ECs chemistry, biochemistry, metabolism, and relationship with cancer.

  1. 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…

  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. The Effects of the Parenting Styles on Social Skills of Children Aged 5-6

    ERIC Educational Resources Information Center

    Kol, Suat

    2016-01-01

    The purpose of this study is to determine the effects of the parenting styles on social skills of children aged 5-6. The problem sentence of the research is; Do the parenting styles' have any effects on social skills of children aged 5-6?. The sub-problems of the research are in the form as; Does the social skills of children aged 5-6 differs from…

  9. 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.

  10. 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.

  11. Distribution and excretion of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) and its metabolites in rats and guinea pigs.

    PubMed

    Ohta, Chiho; Haraguchi, Koichi; Kato, Yoshihisa; Endo, Tetsuya; Kimura, Osamu; Koga, Nobuyuki

    2015-01-01

    4-Hydroxy (OH)-2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) is a polychlorinated biphenyl (PCB) metabolite present in human serum at the highest concentration of the PCB metabolites. Our previous study demonstrated that CB187 was metabolized by rat and guinea pig liver microsomes to the major metabolite 4'-OH-2,2',3,3',5,5',6-heptachlorobiphenyl (CB178), and the two minor metabolites 4-OH-CB187 and 4'-OH-2,2',3,5,5',6-hexachlorobiphenyl (CB151). In this study, the distribution of these metabolites in serum, liver and kidney, and their fecal excretion, were examined in rats and guinea pigs intraperitoneally dosed with CB187. Similarly to the in vitro study, 4'-OH-CB178 was a major metabolite in the liver, serum and feces of both animal species on day 4 after CB187 injection, and the level in the liver was about 20 times higher in untreated guinea pigs than in untreated rats. In addition, 4-OH-CB187, a minor metabolite, was detected in the serum and kidneys, but not in the feces, of both guinea pigs and rats. Another minor metabolite, 4'-OH-CB151, was detected at a lower level only in guinea pig feces; little was found in the serum or liver of either animals. Over the 30d following CB187 injection into guinea pigs, 4'-OH-CB178 and 4-OH-CB187 in the serum was observed at higher level on day 4 and day 16 after injection, respectively. The majority of the 4'-OH-CB178 was rapidly excreted to the feces following unmetabolized CB187, whereas 4-OH-CB187 was not found in guinea pig feces and liver during 30d. These results support previous reports that 4-OH-CB187 is retained persistently in animal blood.

  12. The Effect of Science Activities on Concept Acquisition of Age 5-6 Children Groups

    ERIC Educational Resources Information Center

    Dogru, Mustafa; Seker, Fatih

    2012-01-01

    Present research aims to determine the effect of science activities on concept development of preschool period age 5-6 children groups. Parallel to research objective, qualitative research pattern has been the selected method. Study group comprises of collectively 48 children from 5-6 age group attending to a private education institution in city…

  13. Resolving complex chromosome structures during meiosis: versatile deployment of Smc5/6.

    PubMed

    Verver, Dideke E; Hwang, Grace H; Jordan, Philip W; Hamer, Geert

    2016-03-01

    The Smc5/6 complex, along with cohesin and condensin, is a member of the structural maintenance of chromosome (SMC) family, large ring-like protein complexes that are essential for chromatin structure and function. Thanks to numerous studies of the mitotic cell cycle, Smc5/6 has been implicated to have roles in homologous recombination, restart of stalled replication forks, maintenance of ribosomal DNA (rDNA) and heterochromatin, telomerase-independent telomere elongation, and regulation of chromosome topology. The nature of these functions implies that the Smc5/6 complex also contributes to the profound chromatin changes, including meiotic recombination, that characterize meiosis. Only recently, studies in diverse model organisms have focused on the potential meiotic roles of the Smc5/6 complex. Indeed, Smc5/6 appears to be essential for meiotic recombination. However, due to both the complexity of the process of meiosis and the versatility of the Smc5/6 complex, many additional meiotic functions have been described. In this review, we provide a clear overview of the multiple functions found so far for the Smc5/6 complex in meiosis. Additionally, we compare these meiotic functions with the known mitotic functions in an attempt to find a common denominator and thereby create clarity in the field of Smc5/6 research.

  14. 43 CFR 5.6 - What type of permit conditions may the agency impose?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false What type of permit conditions may the agency impose? 5.6 Section 5.6 Public Lands: Interior Office of the Secretary of the Interior COMMERCIAL FILMING AND SIMILAR PROJECTS AND STILL PHOTOGRAPHY ON CERTAIN AREAS UNDER DEPARTMENT JURISDICTION...

  15. 43 CFR 5.6 - What type of permit conditions may the agency impose?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false What type of permit conditions may the agency impose? 5.6 Section 5.6 Public Lands: Interior Office of the Secretary of the Interior COMMERCIAL FILMING AND SIMILAR PROJECTS AND STILL PHOTOGRAPHY ON CERTAIN AREAS UNDER DEPARTMENT JURISDICTION...

  16. IMMUNOASSAY METHODS FOR MEASURING ATRAZINE AND 3,5,6-TRICHLORO-2-PYRIDINOL IN FOODS

    EPA Science Inventory

    This chapter describes the use of enzyme-linked immunosorbent assay (ELISA) methods for the analysis of two potential environmental contaminants in food sample media, atrazine and 3,5,6-trichloro-2-pyridinol (3,5,6-TCP). Two different immunoassay formats are employed: a magnetic...

  17. 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

  18. 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…

  19. 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…

  20. 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.

  1. Cinical Significance of Androgen Receptor, CK-5/6, KI-67 and Molecular Subtypes in Breast Cancer

    PubMed Central

    Kayahan, Münire; İdiz, Ufuk Oğuz; Gucin, Zuhal; Erözgen, Fazilet; Memmi, Naim; Müslümanoğlu, Mahmut

    2014-01-01

    Objective To detect the relationship between molecular subtypes of breast cancer with expressions of androgen receptor, cytokeratin 5/6 (CK5/6)and Ki-67. Materials and Methods Expressions of androgen receptor, CK-5/6 and Ki-67 were determined by immunohistochemistry in paraffin-embedded sections obtained from 86 invasive breast cancer cases of stages I/IIa/IIb in 4 molecular subtypes. Patients treated for recurrent disease and locally advanced disease were excluded. Results Forty one luminal A cases, ie. positive estrogen receptor(ER) and/or progesteron receptor (PR) with negative epidermal growth factor receptor (HER2), 14 luminal B, ie. positive ER and/or PR and positive HER2, 14 HER2-enriched (HER2+), ie. negative ER and PR with positive HER2, and 17 triple negative (negative ER and PR and HER2) invasive breast cancers were included. Mean follow-up was 17.46±11.70 mo. Androgen receptor-negativity and CK5/6-positivity were significantly more common in HER2+ and triple negative groups. Ki-67 and histological grade were higher in HER2+ group, significantly. Two deaths were triple negative (P=0.04). Androgen receptor-negativity, CK5/6 and Ki-67 status did not affect survival or systemic metastases, significantly. All groups had local recurrences. Local recurrence was significantly associated with androgen receptor-negativity in luminal A and high Ki-67 value in HER2+ groups. Systemic metastases were significantly more common in triple negative and HER2+ groups. Conclusion Molecular subtypes of breast cancer are prognostic and predictive. Androgen receptor is expressed more commonly in luminal subtypes with better prognosis and androgen receptor negativity is associated with development of local recurrence in luminal A cancers.

  2. 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.

  3. 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.

  4. 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

  5. Pathways for Excited State Nonradiative Decay of 5,6-Dihydroxyindole, a Building Block of Eumelanin.

    PubMed

    Datar, Avdhoot; Hazra, Anirban

    2017-03-17

    The photophysics of 5,6-dihydroxyindole (DHI) following excitation to its lowest two optically bright states has been investigated using the complete active space self consistent field method with second order perturbative energy corrections. There is a barrierless pathway for the molecule to relax from the second lowest bright state (2(1)ππ*) to the lowest bright state (1(1)ππ*). The 1(1)ππ* state has a conical intersection with the optically dark 1(1)πσ* state, which further intersects with the ground state along the NH and OH stretching coordinates. Moreover, the 1(1)ππ* has out-of-plane conical intersections with the ground state. For accessing the conical intersections with the ground state, there are energy barriers, which are higher than the available energy following vertical excitation to the lowest bright state. The nature of the calculated deactivation pathways helps interpret the experimentally estimated lifetimes of the lowest two bright states of DHI. The relatively long excited state lifetimes suggests that isolated DHI in monomeric form cannot rationalize the ultrafast deactivation property of eumelanin.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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…

  12. 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…

  13. 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.…

  14. 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…

  15. Brazilian Red Propolis Attenuates Hypertension and Renal Damage in 5/6 Renal Ablation Model

    PubMed Central

    Teles, Flávio; da Silva, Tarcilo Machado; da Cruz Júnior, Francisco Pessoa; Honorato, Vitor Hugo; de Oliveira Costa, Henrique; Barbosa, Ana Paula Fernandes; de Oliveira, Sabrina Gomes; Porfírio, Zenaldo; Libório, Alexandre Braga; Borges, Raquel Lerner; Fanelli, Camilla

    2015-01-01

    The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection. PMID:25607548

  16. Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model.

    PubMed

    Teles, Flávio; da Silva, Tarcilo Machado; da Cruz Júnior, Francisco Pessoa; Honorato, Vitor Hugo; de Oliveira Costa, Henrique; Barbosa, Ana Paula Fernandes; de Oliveira, Sabrina Gomes; Porfírio, Zenaldo; Libório, Alexandre Braga; Borges, Raquel Lerner; Fanelli, Camilla

    2015-01-01

    The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

  17. Comparing earthquake models for the Corinth rift for Mw>=5.5/6/6.5 (Greece)

    NASA Astrophysics Data System (ADS)

    Boiselet, Aurélien; Scotti, Oona; Lyon-Caen, Hélène; Ford, Mary; Meyer, NIcolas; Bernard, Pascal

    2013-04-01

    The Corinth rift (Greece) is identified as a site of major importance for earthquake studies in Europe, producing one of the highest seismic activity and strain in the Euro-Mediterranean region. It is characterized by an asymmetrical structure, with the most active normal faults dipping north and a north-south extension rate measured by GPS increasing from 0.6 mm/year in the eastern part of the rift to 15 mm/year in the western part. Frequent seismic swarms and destructive earthquakes are observed in this area. The Corinth rift Laboratory (CRL, http://crlab.eu) european project investigates fault mechanics, its relationship with earthquakes, fluid flow and the related hazards in the western part of the rift, covering an area about 50 km by 40 km, between the city of Patras to the west and the city of Aigion to the east. As part of this project, within the CRL-SISCOR group, we construct earthquake forecast models (EFM) for M>=5.5/6/6.5 events of the Corinth rift area based on the in-depth seismotectonic studies available for this region. We first present the methodology used to construct the earthquake and fault databases and to quantify the associated uncertainties. We then propose EFM following two approaches: one based on the definition of seimotectonic areas with similar geologic or strain characteristics, the second one based on the definition of fault sources mapped at the surface as well as blind ones. In order to compute the probability of occurrence for M>=5.5/6/6.5 for seismotectonic areas, we analyse two earthquake catalogues available for Greece (National Observatory of Athens, Thessaloniki), apply two declustering methods (Reasenberg and Gardner) to construct a Poissonian earthquake catalogue and test the influence of the minimal magnitude (3.5; 4.0). We compare the impact of maximum magnitude and corner magnitude (Kagan 1997, 2002) estimations. We then apply the Weichert method to estimate the probability of occurrence of M>=5.5/6/6.5 based on

  18. 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

  19. Surveys of Luminous Quasars in the Post-reionization Universe at z=5-6

    NASA Astrophysics Data System (ADS)

    Yang, Jinyi; Wu, Xue-Bing; Fan, Xiaohui; Wang, Feige; McGreer, Ian D.; Bian, Fuyan; Green, Richard F.; Yang, Qian; Jiang, Linhua; Wang, Ran; Yi, Weimin; UHS Team

    2017-01-01

    Quasars at z ~ 5 to 6, the post-reionization epoch, are crucial tools to explore the evolution of intergalactic medium (IGM), quasar evolution and the early super-massive black hole growth. The quasar luminosity function (QLF) and its evolution at z >~ 5 is also needed to estimate the contribution of quasars to the ionizing background during and after the reionization epoch. McGreer et al. (2013) provided the first complete measurement of the z ~ 5 QLF. However, their work focused on faint quasars over a small sky area; there were only 8 quasars with M1450 < -27.3. We have carried out a new quasar survey of luminous quasars at 4.7 < z < 5.4 over 14555 deg^2 with high completeness, selected using a combination of SDSS and WISE optical/NIR colors . Using this luminous z ~ 5 quasar sample, we present a new determination of the z ~ 5 QLF and discuss the evolution model of QLF at high redshift. Based on surveys of luminous quasars at z > 4, previous studies have concluded that the number density evolution steepens at high redshift, such that luminous quasars decline as a population more steeply at higher redshift (z ~ 5.5) than from z=4 to 5. However, quasars at redshifts 5.3 < z < 5.7 have been very challenging to select using conventional color selections, due to their similar optical colors to late-type stars, especially M dwarfs, resulting in a glaring redshift gap in quasar redshift distribution. We have developed a new selection technique for z ~ 5.5 quasars based on optical, near- and mid-infrared photometric data. Up to date, we have constructed an uniform luminous z ~ 5.5 quasar sample with 26 new quasars. Our final completed sample of quasars at z=5-6 will be used to study QLF, evolution model and IGM evolution in the post-deionization universe.

  20. 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.

  1. 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.

  2. Effect of thalidomide on tumour necrosis factor production and anti-tumour activity induced by 5,6-dimethylxanthenone-4-acetic acid.

    PubMed Central

    Ching, L. M.; Xu, Z. F.; Gummer, B. H.; Palmer, B. D.; Joseph, W. R.; Baguley, B. C.

    1995-01-01

    The investigational anti-tumour agent, 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), an analogue of flavone acetic acid (FAA), has been scheduled for clinical evaluation. Like FAA, 5,6-MeXAA exhibits excellent experimental anti-tumour activity and is an efficient inducer of cytokines in mice. We have examined the effect of pharmacological suppression of tumour necrosis factor (TNF) production on the anti-tumour activity of 5,6-MeXAA, taking advantage of previous observations that TNF production in response to endotoxin in vitro is inhibited by thalidomide. Thalidomide at doses of between 8 and 250 mg kg-1 efficiently suppressed serum TNF activity in response to 5,6-MeXAA at its optimal TNF inducing dose of 55 mg kg-1. Suppression was achieved when thalidomide was administered at the same time as, or up to 4 h before, 5,6-MeXAA. Under conditions in which TNF activity was suppressed, the degree of tumour haemorrhagic necrosis and the proportion of cures in the subcutaneous Colon 38 tumour were increased. In mice administered thalidomide (100 mg kg-1) together with 5,6-MeXAA (30 mg kg-1), complete tumour regression was obtained in 100% of mice, as compared with 67% in mice receiving 5,6-MeXAA alone. The results suggest a possible new application for thalidomide and pose new questions about the action of 5,6-MeXAA and related compounds. PMID:7640215

  3. Acetato(1,10-phenanthroline-5,6-dione)silver(I) trihydrate

    PubMed Central

    Onuegbu, Jonathan; Butcher, Ray J.; Hosten, Charles; Udeochu, Uche Charles; Bakare, Oladapo

    2008-01-01

    In the structure of the title compound, [Ag(C2H3O2)(C12H6N2O2)]·3H2O, the AgI atom is coordinated by both 1,10-phenanthroline-5,6-dione N atoms and one O atom from the acetate anion. The three water mol­ecules are involved in extensive hydrogen bonding to each other and to the acetate O and 1,10-phenanthroline-5,6-dione O atoms. In addition, there are weak C—H⋯O inter­actions. PMID:21201351

  4. 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.

  5. 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…

  6. 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

  7. Decadally resolved quantitative temperature reconstruction spanning 5.6 ka at Kurupa Lake, Arctic Alaska

    NASA Astrophysics Data System (ADS)

    Boldt, B. R.; Kaufman, D. S.; Briner, J. P.

    2012-12-01

    authenticate the model over the limited calibration period and to estimate the uncertainty of prediction (RMSEP = 0.8°C); the uncertainty estimate does not account for changes in the relation between temperature and pigment concentration through time (non-stationarity). Our chlorophyll-a-inferred temperature reconstruction (50-year smoothed) shows minimum summer temperature (ΔT -2.7 ± 0.8°C relative to the 1961-1990 reference period) at 660 AD and maximum summer temperature (ΔT = +2.3 ± 0.8°C) during the most recent decade. Despite the decrease in northern hemisphere insolation, there is no apparent overall cooling trend through the record. The middle and late Holocene temperatures were punctuated by warmer periods at 3390-2040 cal BP and 710-1060 AD (during the Medieval Climate Anomaly), and by colder temperatures 1110-1310 AD and 1660-1910 AD (a two-phase Little Ice Age). Our temperature reconstruction displays synchronous changes with independent paleoclimatic proxies from elsewhere in Arctic Alaska (e.g., Anderson and Abbott, 2001; Bird et al., 2009), and indicates that the last century was warmer than anytime during the last 5.6 ka.

  8. DETERMINATION OF 3,5,6-TRICHLORO-2-PYRIDINOL (TCP) BY ELISA

    EPA Science Inventory

    A sensitive, competitive enzyme-linked immunosorbent assay (ELISA) for 3,5,6-trichloro-2pyridinol (TCP) has been developed to quantitate parts per billion (ppb) amounts of the analyte in urine. TCP is a major metabolite and environmental degradation product of the insecticide c...

  9. Can 5-6 Year Old Children Orientate Themselves in a Cave?

    ERIC Educational Resources Information Center

    Jovignot, Francois

    1995-01-01

    Spatial capacities of 36 children ages 5-6 were tested in 3 experiments involving an electronic maze, map training and testing, and finding the way out of a cave using a map. All subjects could use simple maps; this ability improved with age. However, no subject navigated the cave without help, perhaps because of stress or task complexity. (SV)

  10. Regioselective Glycosylation of 3-, 5-, 6-, and 7-Hydroxyflavones by Cultured Plant Cells.

    PubMed

    Shimoda, Kei; Kubota, Naoji; Uesugi, Daisuke; Fujitaka, Yuuya; Okada, Shouta; Tanigawa, Masato; Hamada, Hiroki

    2015-06-01

    Regioselective glycosylation of 3-, 5-, 6-, and 7-hydroxyflavones was investigated using cultured plant cells of Eucalyptus perriniana and Phytolacca americana as biocatalysts. 3- and 7-Hydroxyflavones were practically glycosylated into the corresponding β-D-glucosides by E. perriniana and P. americana.

  11. The SMC5/6 complex is involved in crucial processes during human spermatogenesis.

    PubMed

    Verver, Dideke E; Langedijk, Nathalia S M; Jordan, Philip W; Repping, Sjoerd; Hamer, Geert

    2014-07-01

    Genome integrity is crucial for safe reproduction. Therefore, chromatin structure and dynamics should be tightly regulated during germ cell development. Chromatin structure and function are in large part determined by the structural maintenance of chromosomes (SMC) protein complexes, of which SMC5/6 recently has been shown to be involved in both spermatogonial differentiation and meiosis during mouse spermatogenesis. We therefore investigated the role of this complex in human spermatogenesis. We found SMC6 to be expressed in the human testis and present in a subset of type Adark and type Apale spermatogonia, all spermatocytes, and round spermatids. During human meiosis, SMC5/6 is located at the synaptonemal complex (SC), the XY body, and at the centromeres during meiotic metaphases. However, in contrast to mouse spermatogenesis, SMC6 is not located at pericentromeric heterochromatin in human spermatogenic cells, indicating subtle but perhaps important differences in not only SMC5/6 function but maybe also in maintenance of genomic integrity at the repetitive pericentromeric regions. Nonetheless, our data clearly indicate that the SMC5/6 complex, as shown in mice, is involved in numerous crucial processes during human spermatogenesis, such as in spermatogonial development, on the SC between synapsed chromosomes, and in DNA double-strand break repair on unsynapsed chromosomes during pachynema.

  12. Viscosity Measurements of Eclogite Melt up to 5.6 GPa and 2000 K

    NASA Astrophysics Data System (ADS)

    Liu, H.; Fei, Y.; Han, L.; Kono, Y.; Hou, M.; Zhao, Z.; Du, J.

    2014-12-01

    The melting and rheology of eclogite is critical for understanding the dynamics of the subduction zone and plate tectonic. Viscosity of eclogite melt as a function of depth is a key parameter to model the long-term chemical evolution of the subduction zone and volcanic magma. It also plays an important role in earthquakes and continent formation. However, the viscosity and rheology of eclogite melt remain poorly understood at high pressure and temperature. In this study, we have carried out in-situ falling-sphere viscometry measurements to determine the viscosity of eclogite melt from 1.3 to 5.6 GPa at temperatures between 1500 and 2000 K, using the Paris-Edinburgh cell at the 16-BM-B beamline of the High Pressure Collaborative Access Team (HPCAT) at the Advanced Photon Source. We used a natural eclogite sample with 47.7wt% SiO2. The viscosity (η) was calculated with the Stokes' equation. The viscosity of eclogite melt decreases between 1.3 and 5.6 GPa at 2000K. At 1.4 GPa and 2000K the viscosity is 0.43 Pa·s, whereas at 5.6 GPa and 2000 K it is 0.13Pa·s. No minimum in the viscosity of eclogite was found in the measured pressure range up to 5.6 GPa.

  13. The Effects of Folk Dance Training on 5-6 Years Children's Physical and Social Development

    ERIC Educational Resources Information Center

    Biber, Kazim

    2016-01-01

    The purpose of this study is to analyze the effects of folk dance training on 5-6 year old Pre-school children's physical and social development. The experimental design with an experimental and control group was used in accordance with the quantitative research methods in this research. The research has been conducted with the participation of 40…

  14. The structure and properties of 5,6-dinitro-1H-benzotriazole

    NASA Astrophysics Data System (ADS)

    Santa María, Dolores; Claramunt, Rosa M.; Torralba, M. Carmen; Torres, M. Rosario; Alkorta, Ibon; Elguero, José

    2016-06-01

    5,6-Dinitro-1H-benzotriazole crystallizes in the monoclinic system, space group P21/c. The asymmetric unit contains the planar 1H-tautomer together with a water molecule of crystallization. Each water molecule is hydrogen bonded to three adjacent 5,6-dinitrobenzotriazoles forming a tape along the b-axis of the crystal. These tapes stack along the c-axis through hydrogen bonds involving the water molecules and one of the nitro groups leading to a bidimensional structure. Solid-state 13C and 15N CPMAS NMR allow to confirm that the tautomer present is the 1H one. In DMSO-d6 solution the results are quite different and, based on GIAO/B3LYP/6-311++G(d,p) calculations, lead us to conclude that the major tautomer is the 5,6-dinitro-2H-benzotriazole, a surprising result that contradicts the rule that the major tautomer in solution coincides with the one present in the crystal. An anhydrous pseudopolymorph of 5,6-dinitro-1H-benzotriazole has been obtained as a non-crystalline form and from solid-state NMR and theoretical calculations, we conclude that it is an 1H-tautomer.

  15. 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.

  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. 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

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

    PubMed Central

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

    2012-01-01

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

  19. 5,6-Diphenylpyridazine derivatives as acyl-CoA:cholesterol acyltransferase inhibitors.

    PubMed

    Giovannoni, M P; Piaz, V D; Kwon, B M; Kim, M K; Kim, Y K; Toma, L; Barlocco, D; Bernini, F; Canavesi, M

    2001-11-22

    Alkyl-5,6-diphenylpyridazine derivatives combining several main features of ACAT inhibitors, such as a long alkyl side chain linked to a heterocycle and the o-diphenyl system, were synthesized and tested. Moreover, modeling studies on representative terms were performed. Some compounds displayed ACAT inhibition in the micromolar range, both on the enzyme isolated from rat liver microsomes and in cell-free homogenate of murine macrophages.

  20. The Diaza[5.5.6.6]fenestrane Skeleton-Synthesis of Leuconoxine Alkaloids.

    PubMed

    Pfaffenbach, Magnus; Gaich, Tanja

    2016-03-07

    Among the Aspidosperma-derived monoterpene indole alkaloids, the leuconoxine subgroup has drawn significant attention from the synthetic community during the past few years. This Minireview summarizes the hitherto six completed total syntheses of leuconoxines emphasizing the different strategies for assembling the key structural motif, an unprecedented diaza[5.5.6.6]fenestrane skeleton. In addition, the proposed biogenetic relationships within the group of these alkaloids are described.

  1. 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.

  2. The Extracellular Domain of Lrp5/6 Inhibits Noncanonical Wnt Signaling In Vivo

    PubMed Central

    Andersson, Emma R.; Schambony, Alexandra; Esner, Milan; Bryjová, Lenka; Biris, Kristin K.; Hall, Anita C.; Kraft, Bianca; Cajanek, Lukas; Yamaguchi, Terry P.; Buckingham, Margaret

    2009-01-01

    Lrp5/6 are crucial coreceptors for Wnt/β-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of Lrp5/6 in noncanonical Wnt signaling. We found that Lrp6 physically interacts with Wnt5a, but that this does not lead to phosphorylation of Lrp6 or activation of the Wnt/β-catenin pathway. Overexpression of Lrp6 blocks activation of the Wnt5a downstream target Rac1, and this effect is dependent on intact Lrp6 extracellular domains. These results suggested that the extracellular domain of Lrp6 inhibits noncanonical Wnt signaling in vitro. In vivo, Lrp6−/− mice exhibited exencephaly and a heart phenotype. Surprisingly, these defects were rescued by deletion of Wnt5a, indicating that the phenotypes resulted from noncanonical Wnt gain-of-function. Similarly, Lrp5 and Lrp6 antisense morpholino-treated Xenopus embryos exhibited convergent extension and heart phenotypes that were rescued by knockdown of noncanonical XWnt5a and XWnt11. Thus, we provide evidence that the extracellular domains of Lrp5/6 behave as physiologically relevant inhibitors of noncanonical Wnt signaling during Xenopus and mouse development in vivo. PMID:19056682

  3. 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.

  4. 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.

  5. 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

  6. Development of a high-resolution record of Great Basin climate change during MIS 5, 6, and 7

    NASA Astrophysics Data System (ADS)

    Cross, M.; McGee, D.; Broecker, W. S.; Quade, J.; Cheng, H.; Edwards, R.

    2013-12-01

    As evinced by the cycles of the large paleolakes Lahontan and Bonneville, the currently semi-arid to arid Great Basin region of the United States has experienced significant changes in climate and water balance in the past. Although there has been substantial research concerning these changes for times around and since the last glacial maximum, relatively little is known about the region's previous climate and water balance history. There is a clear need for a long-term record for earlier glacial and interglacial periods. Here, we present some of our initial results from Lehman Cave (39.01°N, 114.22°W), a well-decorated, active cave located on the edge of the Bonneville Basin in the Great Basin National Park, for times correlating with large portions of Marine Oxygen Isotope Stages (MIS) 5, 6, and 7. We initially surveyed a suite of speleothems to obtain times and durations of growth phases to aid in choosing samples appropriate for more extensive analysis. Approximately eighty 2 to 10 mg samples with a mean 238U of 400 ppb, representing most of the major growth phases of this suite of 20 speleothems, were analyzed for preliminary uranium-thorium dates. A subset of eight of these stalagmites grew collectively over large portions of MIS 5 and 6 (an interval that includes the Little Valley lake cycle of the Bonneville Basin) as well as a substantial portion of MIS 7. This record includes several significant periods of contemporaneous growth, including: 81.5 to 103 ka, which corresponds to the interval between Dansgaard-Oeschger events 21 and 23; 204 to 207 ka; and 118 to 132 ka, an interval including the beginning of the last interglacial period and the end of Termination II and Heinrich Stadial 11. We have yet to identify growth phases between 103 to 118 ka, 134 to 137 ka, and 164 to 169 ka. Initial stable isotope results indicate a shift of approximately +3‰ δ18O and +5‰ δ13C around 131 × 2.5 ka, which agrees within error with the findings of Shakun et al

  7. Novel synthesis of silver nanoparticles using 2,3,5,6-tetrakis-(morpholinomethyl) hydroquinone as reducing agent.

    PubMed

    Manivel, P; Balamurugan, A; Ponpandian, N; Mangalaraj, D; Viswanathan, C

    2012-09-01

    2,3,5,6-Tetrakis-(morpholinomethyl) hydroquinone (TMMH) was used as a reducing agent to synthesize spherical shaped silver nanoparticles in water-ethanol medium without using any stabilizing and capping agents. The reducing agent TMMH is prepared by Mannich-type reaction method and (1)H NMR, (13)C NMR and FT-IR spectroscopy techniques were used to characterize the compound (TMMH). The nature of bonding, structural and optical properties of the final product were analyzed using different techniques such as UV-Vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The interaction between silver and reducing agent was confirmed by using FTIR analysis. The final product obtained showed higher crystallinity with cubic structure and an average crystalline size of about 20 nm. The results revealed that it is possible to synthesize crystalline Ag nanoparticles using organic compound as reducing agent.

  8. Novel synthesis of silver nanoparticles using 2,3,5,6-tetrakis-(morpholinomethyl) hydroquinone as reducing agent

    NASA Astrophysics Data System (ADS)

    Manivel, P.; Balamurugan, A.; Ponpandian, N.; Mangalaraj, D.; Viswanathan, C.

    2,3,5,6-Tetrakis-(morpholinomethyl) hydroquinone (TMMH) was used as a reducing agent to synthesize spherical shaped silver nanoparticles in water-ethanol medium without using any stabilizing and capping agents. The reducing agent TMMH is prepared by Mannich-type reaction method and 1H NMR, 13C NMR and FT-IR spectroscopy techniques were used to characterize the compound (TMMH). The nature of bonding, structural and optical properties of the final product were analyzed using different techniques such as UV-Vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The interaction between silver and reducing agent was confirmed by using FTIR analysis. The final product obtained showed higher crystallinity with cubic structure and an average crystalline size of about 20 nm. The results revealed that it is possible to synthesize crystalline Ag nanoparticles using organic compound as reducing agent.

  9. 5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes. A Nucleophilic Displacement Route

    PubMed Central

    Krow, Grant R.; Edupuganti, Ram; Gandla, Deepa; Choudhary, Amit; Lin, Guoliang; Sonnet, Philip E.; DeBrosse, Charles; Ross, Charles W.; Cannon, Kevin C.; Raines, Ronald T.

    2012-01-01

    Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position. PMID:19799411

  10. 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

  11. Differential renal glomerular changes induced by 5/6 nephrectomization between common marmoset monkeys (Callithrix jacchus) and rats.

    PubMed

    Suzuki, Yui; Yamaguchi, Itaru; Onoda, Noriko; Saito, Takashi; Myojo, Kensuke; Imaizumi, Minami; Takada, Chie; Kimoto, Naoya; Takaba, Katsumi; Yamate, Jyoji

    2013-07-01

    We have been investigating the relevance and availability of 5/6 nephrectomized (Nx) common marmoset monkeys (Callithrix jacchus) as a chronic renal failure model. As a part of this investigation, renal glomerular changes in the Nx marmosets were histopathologically and immunohistochemically evaluated, and then compared with those in 5/6 Nx SD rats. In the Nx marmosets, the blood and urine parameters were elevated, excluding urine protein; histopathologically, enlargement of Bowman's capsule and atrophy of the glomeruli were observed in all animals, and other slight changes were also observed in 1 or 2 marmosets. There were no significant changes in the mesangial matrix injury score, vimentin and desmin positivity or the number of WT1 positive cells between the control and Nx marmoset groups. On the other hand, in the Nx rats, the blood and urine parameters were elevated; histopathologically, various changes were observed in the glomeruli, and the mesangial matrix injury score, vimentin and desmin positivity were increased, while the number of WT1 positive cells was decreased; these histopathological impacts on the renal glomerulus at 13 weeks after Nx in rats were more severe than that in the Nx marmosets. Because the glomerular basement membrane (GBM) was much thicker in the marmosets than in the rats in electron microscopy, the weaker pathological changes in the Nx marmosets might be due to the GBM thickness. This study showed for the first time glomerular lesions developed in the Nx marmosets, and the possible pathogenesis of the glomerular lesions was discussed.

  12. Renal endothelial function is associated with the anti-proteinuric effect of ACE inhibition in 5/6 nephrectomized rats.

    PubMed

    Vettoretti, Simone; Vavrinec, Peter; Ochodnicky, Peter; Deelman, Leo E; De Zeeuw, Dick; Henning, Rob H; Buikema, Hendrik

    2016-05-01

    In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started (n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria (r(2) = 0.648, P = 0.003) and with the decrease in SBP (r(2) = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.

  13. Several (4,4)- and (5,6,8)-connected lanthanide-organic frameworks: structures, luminescence and magnetic properties.

    PubMed

    Zhao, Xiao-Qing; Liu, Xu-Hui; Zhao, Bin

    2013-10-01

    A series of lanthanide-based organic frameworks with formulas of {[PrL(H2O)2]·2H2O}n () and {[Ln3L3(H2O)2]·2H2O}n (Ln = Eu (), Gd (), Tb (), Dy (), Ho (), Er (); H3L = 4-(carboxymethoxy)isophthalic acid), were hydrothermally synthesized and structurally characterized. It is the first time that 4-(carboxymethoxy)isophthalic acid is employed in producing lanthanide compounds. The seven compounds exhibit two types of structures with the decreasing radius of the lanthanide ions, representing the lanthanide contraction effect. Compound with the large Pr(3+) ion displays a 2D layered structure with a binodal (4,4)-connected topology with the Schläfli symbol of (3(3)6(3))2, whereas compounds with small Ln(3+) ions feature a 3D framework constructed from carboxyl groups with a (5,6,8)-connected topology with the Schläfli symbol of (3(2)4(4)5(4))·(3(4)4(4)5(4)6(3))·(3(4)4(8)5(6)6(9)8). The luminescence and magnetic properties were investigated, and the results indicate that the H3L ligand can sensitize the lanthanide luminescence in compounds , and and makes a contribution to the antiferromagnetic interactions in compound or the uncertain magnetic interactions in compounds . Additionally, the thermal analyses suggest the high thermal stability of compounds .

  14. Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development.

    PubMed

    Benito-Sipos, Jonathan; Ulvklo, Carina; Gabilondo, Hugo; Baumgardt, Magnus; Angel, Anna; Torroja, Laura; Thor, Stefan

    2011-12-01

    Drosophila embryonic neuroblasts generate different cell types at different time points. This is controlled by a temporal cascade of Hb→Kr→Pdm→Cas→Grh, which acts to dictate distinct competence windows sequentially. In addition, Seven up (Svp), a member of the nuclear hormone receptor family, acts early in the temporal cascade, to ensure the transition from Hb to Kr, and has been referred to as a 'switching factor'. However, Svp is also expressed in a second wave within the developing CNS, but here, the possible role of Svp has not been previously addressed. In a genetic screen for mutants affecting the last-born cell in the embryonic NB5-6T lineage, the Ap4/FMRFamide neuron, we have isolated a novel allele of svp. Expression analysis shows that Svp is expressed in two distinct pulses in NB5-6T, and mutant analysis reveals that svp plays two distinct roles. In the first pulse, svp acts to ensure proper downregulation of Hb. In the second pulse, which occurs in a Cas/Grh double-positive window, svp acts to ensure proper sub-division of this window. These studies show that a temporal factor may play dual roles, acting at two different stages during the development of one neural lineage.

  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. Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer.

    PubMed

    Maeda, Tetsuyo; Nakanishi, Yoko; Hirotani, Yukari; Fuchinoue, Fumi; Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao; Nemoto, Norimichi

    2016-03-01

    RNA expression was higher in patients with AR-negative TNBC (P < 0.05) and in patients with the worst prognosis (P < 0.05) than in the other patients. These results suggested that, in patients with CK5/6-negative TNBC, AR expression correlated with good prognosis, but p53 accumulation correlated with poor prognosis. The present IHC markers allowed us to predict the post-surgery prognosis of patients with TNBC. In conclusion, TNBCs are heterogeneous. Patients with the CK5/6 (-), AR (-), and p53 (+) TNBC subtype, evaluated by IHC, presented the worst prognosis. These IHC markers will be helpful to follow patients with TNBC.

  17. Vaccine-Induced Anti-HBs Level in 5-6 Year-Old Malnourished Children

    PubMed Central

    Karimi, Mehran; Raee, Ali; Baghianimoghadam, Behnam; Fallahzadeh, Mohammad Hossein

    2013-01-01

    Background Malnutrition is the most common cause of immune deficiency. It results in reduced secretion of T-cells and B-cell-stimulating factors leading to declining of special immunoglobulins. On the other hand, hepatitis B, as a major world health problem, can be prevented effectively by vaccination. Three doses of hepatitis B virus (HBV) vaccine induce protective levels of anti-hepatitis B surface (anti-HBs) in 95% of healthy children. This level decreases gradually over time. Objectives The goal of this study was to assess anti-HBs in malnourished children, who confronted to some degrees of immune deficiency. Patients and Methods This is a cross-sectional study conducted during May to August 2010 in therapeutic clinics of Yazd, Iran. Samples were selected simply and consecutively among 5-6 year-old children with a history of three doses of HBV vaccine in infancy. On the basis of World Health Organization’s definition on malnutrition, which considers anthropometric measurements, malnourished children entered the study. Totally 83 cases (37 boys and 46 girls) were gathered and classified into three groups of mild, moderate, and severe malnutrition. One milliliter of venous blood was taken and anti-HBs were tested by enzyme linked immunosorbant assay (ELISA). Results Overall, seroprotection rate and geometric mean titer (GMT) of anti-HBs were 60.2% and 15.47 ± 10.92 mIU/mL, respectively. Seroprotection rate was 71.4%, 55.2%, and 72.7% in mild, moderate, and severe malnourished children, respectively. GMT was 30.78 mIU/mL, 12.15 mIU/mL, and 22.95 mIU/mL in these groups, respectively. None of these two indices were significant in these groups (P = 0.471, P = 0.364). Seroprotection rate and GMT were 54.1% and 13.26 ± 11.59 mIU/mL in boys, and 65.2% and 17.5 ± 10.59 mIU/mL in girls, respectively, showing no significant relationship with gender (P = 0.302, P = 0.602). Lowest seroprotection rate was in stunted cases (47.1%) and highest in wasted children (77

  18. Texture in a ternary Nd 16.2Fe 78.2B 5.6 powder using a modified hydrogenation-disproportionation-desorption-recombination process

    NASA Astrophysics Data System (ADS)

    Gutfleisch, O.; Gebel, B.; Mattern, N.

    2000-02-01

    A modified hydrogenation-disproportionation desorption-recombination (HDDR) process consisting of (i) solid disproportionation and (ii) slow recombination under partial hydrogen pressure has been applied to a Nd 16.2Fe 78.2B 5.6 alloy. Scanning electron microscopy shows that an initially fine rod-like structure of NdH 2± x and Fe observed after 15 min of hydrogenation at 900°C is transformed into a granular morphology with prolonged annealing. Simultaneously, finely dispersed tetragonal Fe 3B particles of 10-50 nm diameter exist. XRD studies show that this metastable Fe 3B phase is transformed to Fe 2B and Fe on further annealing. Short solid-disproportionation times result in a higher degree of anisotropy after recombination, whereas long annealing times and conventional processing lead to isotropic material. It is concluded that the formation of the intermediate tetragonal Fe 3B phase after solid disproportionation is pivotal for the inducement of texture in HDDR processed ternary NdFeB-type alloys.

  19. Readiness Review of BWXT for Fabrication of AGR-5/6/7 TRISO Particles

    SciTech Connect

    Marshall, Douglas William; Sharp, Michelle Tracy

    2016-02-01

    INL readiness review assessment of BWXT readiness to commence fabrication of low-enriched TRISO coated fuel particles for the AGR-5/6/7 irradiation experiments. BWXT self-identified equipment issues preventing operation. INL identified two findings. The first was that disposition codes had not been assigned and documented on BWXT forms to ensure that off-specification materials could not be used in the fabrication of TRISO particles. The second was that chemical purity specifications were not reliably passed on to chemical suppliers, which resulted in the receipt of one acetylene cylinder with suspect impurity levels.

  20. Rare-earth plasma extreme ultraviolet sources at 6.5-6.7 nm

    SciTech Connect

    Otsuka, Takamitsu; Higashiguchi, Takeshi; Yugami, Noboru; Yatagai, Toyohiko; Kilbane, Deirdre; White, John; Dunne, Padraig; O'Sullivan, Gerry; Jiang, Weihua; Endo, Akira

    2010-09-13

    We have demonstrated a laser-produced plasma extreme ultraviolet source operating in the 6.5-6.7 nm region based on rare-earth targets of Gd and Tb coupled with a Mo/B{sub 4}C multilayer mirror. Multiply charged ions produce strong resonance emission lines, which combine to yield an intense unresolved transition array. The spectra of these resonant lines around 6.7 nm (in-band: 6.7 nm {+-}1%) suggest that the in-band emission increases with increased plasma volume by suppressing the plasma hydrodynamic expansion loss at an electron temperature of about 50 eV, resulting in maximized emission.

  1. 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.

  2. Analysis of a Near Field MIMO Wireless Channel Using 5.6 GHz Dipole Antennas

    NASA Astrophysics Data System (ADS)

    Maricar, Mohamed Ismaeel; Gradoni, Gabriele; Greedy, Steve; Ivrlac, Michel T.; Nossek, Josef A.; Phang, Sendy; Creagh, Stephen C.; Tanner, Gregor; Thomas, David W. P.

    2016-05-01

    Understanding the impact of interference upon the performance of a multiple input multiple output (MIMO) based device is of paramount importance in ensuring a design is both resilient and robust. In this work the effect of element-element interference in the creation of multiple channels of a wireless link approaching the near-field regime is studied. The elements of the 2-antenna transmit- and receive-arrays are chosen to be identical folded dipole antennas operating at 5.6 GHz. We find that two equally strong channels can be created even if the antennas interact at sub-wavelength distances, thus confirming previous theoretical predictions.

  3. 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.

  4. Smc5/6-Mms21 Prevents and Eliminates Inappropriate Recombination Intermediates in Meiosis

    PubMed Central

    Xaver, Martin; Huang, Lingzhi; Chen, Doris; Klein, Franz

    2013-01-01

    Repairing broken chromosomes via joint molecule (JM) intermediates is hazardous and therefore strictly controlled in most organisms. Also in budding yeast meiosis, where production of enough crossovers via JMs is imperative, only a subset of DNA breaks are repaired via JMs, closely regulated by the ZMM pathway. The other breaks are repaired to non-crossovers, avoiding JM formation, through pathways that require the BLM/Sgs1 helicase. “Rogue” JMs that escape the ZMM pathway and BLM/Sgs1 are eliminated before metaphase by resolvases like Mus81-Mms4 to prevent chromosome nondisjunction. Here, we report the requirement of Smc5/6-Mms21 for antagonizing rogue JMs via two mechanisms; destabilizing early intermediates and resolving JMs. Elimination of the Mms21 SUMO E3-ligase domain leads to transient JM accumulation, depending on Mus81-Mms4 for resolution. Absence of Smc6 leads to persistent rogue JMs accumulation, preventing chromatin separation. We propose that the Smc5/6-Mms21 complex antagonizes toxic JMs by coordinating helicases and resolvases at D-Loops and HJs, respectively. PMID:24385936

  5. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

    PubMed Central

    van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

    2016-01-01

    The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

  6. 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

  7. Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone (coumarin).

    PubMed Central

    Casley-Smith, J R; Wang, C T; Casley-Smith, J R; Zi-hai, C

    1993-01-01

    OBJECTIVE--To study efficacy of treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone. DESIGN--Randomised, double blind, placebo controlled study with matching for grade and duration of disease, age, and sex. Treatment was given for 367 days, and subjects were followed up for another year. SETTING--A town in Shandong Province, China. SUBJECTS--104 men and women with chronic unilateral filarial lymphoedema or elephantiasis of the leg: 64 were randomised to benzopyrone and 40 to placebo. By the end of the study 19 patients had dropped out of the treatment group and two out of the placebo group. INTERVENTIONS--Two 200 mg tablets of 5,6-benzo-alpha-pyrone or two placebo tablets given daily. MAIN OUTCOME MEASURES--Volumes of the affected and normal legs estimated every three months, and daily listing of any side effects. RESULTS--Benzopyrone reduced oedema for all grades of lymphoedema during the year of treatment (pW0.001) and the follow up year (p = 0.026). During treatment the mean monthly reductions in leg volume were 0.62% (95% confidence intervals 0.4% to 0.85%), 1.1% (0.71% to 1.6%), and 1.6% (0.89% to 2.3%) of the volume of the normal leg for grades 1, 2, and 3-5 (elephantiasis) of lymphoedema respectively. During follow up the mean monthly reductions were 0.18% (0.01% to 0.35%), 0.54% (0.27% to 0.82%), and 0.87% (0.51% to 1.2%). At the end of the trial the total reduction in oedema was 100%, 95%, and 45% for grades 1, 2, and 3-5. Symptoms and complications were considerably reduced, including attacks of secondary acute inflammation, while side effects were minor and disappeared after one month. In the placebo group there were no changes in the severity of lymphoedema. CONCLUSIONS--5,6-benzo-alpha-pyrone reduces the oedema and many symptoms of filarial lymphoedema and elephantiasis. It has few side effects, and its relatively slow action makes it ideal for use without compression garments. PMID:8251778

  8. 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…

  9. Rigid 5'-6-locked phenanthroline-derived nucleosides chelated to ruthenium and europium ions.

    PubMed

    Gislason, Kristmann; Sigurdsson, Snorri Th

    2013-01-01

    We describe complexes of ruthenium and europium with rigid, 5'-6-locked 1,10-phenanthroline-containing nucleosides. Both nucleosides were synthesized from condensation of 5-amino-2'-deoxycytidine with the corresponding diketone. The ruthenium nucleoside displayed fluorescence characteristic of polypyridine ruthenium complexes with a maximum at 616 nm and a quantum yield of 0.011. Binding of europium to the 1,10-phenanthroline-2,9-diacid moiety of the lanthanide binding nucleoside showed formation of a 1:1 complex with emission at 570-630 nm, whose emission was enhanced by addition of two phenanthroline ligands. The lanthanide-binding nucleoside was incorporated into DNA oligonucleotides and shown to selectively bind one equivalent of europium ions.

  10. Sodium 3,5,6-trichloropyridin-2-ol poisoning: report of four cases.

    PubMed

    Niu, Ying-Mei; Hao, Feng-Tong; Xia, Yu-Jing

    2014-06-01

    Sodium 3,5,6-trichloropyridin-2-ol (STCP) is an important intermediate for synthesizing organophosphate insecticide chlorpyrifos. At present, chlorpyrifos is one of the world's largest species of pesticide products. Many studies have focused on the toxicity of chlorpyrifos, but few reports have looked at the toxicity mechanism of STCP. Even fewer studies have looked at STCP poisoning. With increasing production and usage of STCP, the chances of such poisoning will increase. In this study, we present a report on four workers who helped in the industrial manufacture of STCP and who were affected by exposure to it. We hope that these case studies will provide a foundation for further research into STCP.

  11. Sequential Injection/Electrochemical Immunoassay for Quantifying the Pesticide Metabolite 3, 5, 6-Trichloro-2-Pyridinol

    SciTech Connect

    Liu, Guodong; Riechers, Shawn L.; Timchalk, Chuck; Lin, Yuehe

    2005-12-04

    An automated and sensitive sequential injection electrochemical immunoassay was developed to monitor a potential insecticide biomarker, 3, 5, 6-trichloro-2-pyridinol. The current method involved a sequential injection analysis (SIA) system equipped with a thin-layer electrochemical flow cell and permanent magnet, which was used to fix 3,5,6-trichloro-2-pyridinol (TCP) antibody coated magnetic beads (TCP-Ab-MBs) in the reaction zone. After competitive immunoreactions among TCP-Ab-MBs, TCP analyte, and horseradish peroxidase (HRP) labeled TCP, a 3, 3?, 5, 5?-tetramethylbenzidine dihydrochloride and hydrogen peroxide (TMB-H2O2) substrate solution was injected to produce an electroactive enzymatic product. The activity of HRP tracers was monitored by a square wave voltammetric scanning electroactive enzymatic product in the thin-layer flow cell. The voltammetric characteristics of the substrate and the enzymatic product were investigated under batch conditions, and the parameters of the immunoassay were optimized in the SIA system. Under the optimal conditions, the system was used to measure as low as 6 ng L-1 (ppt) TCP, which is around 50-fold lower than the value indicated by the manufacturer of the TCP RaPID Assay? kit (0.25 ug/L, colorimetric detection). The performance of the developed immunoassay system was successfully evaluated on tap water and river water samples spiked with TCP. This technique could be readily used for detecting other environmental contaminants by developing specific antibodies against contaminants and is expected to open new opportunities for environmental and biological monitoring.

  12. Geomechanical modeling of the nucleation process of Australia's 1989 M5.6 Newcastle earthquake

    NASA Astrophysics Data System (ADS)

    Klose, Christian D.

    2007-04-01

    Inherent to black-coal mining in New South Wales (Australia) since 1801, the discharge of ground water may have triggered the M5.6 Newcastle earthquake in 1989. 4-dimensional geomechanical model simulations reveal that widespread water removal and coal as deep as a 500 m depth resulted in an unload of the Earth's crust. This unload caused a destabilization process of the pre-existing Newcastle fault in the interior of the crust beneath the Newcastle coal field. In tandem, an increase in shear stress and a decrease in normal stress may have reactivated this reverse fault. Over the course of the last fifty years, elevated levels of lithostatic stress alterations have accelerated. In 1991, based on the modeling of the crust's elastostatic response to the unload, there has been the minimal critical shear stress changes of 0.01 Mega Pascal (0.1 bar) that reached the Newcastle fault at a depth where the 1989 mainshock nucleated. Hence, it can be anticipated that other faults might also be critically stressed in that region for a couple of reasons. First, the size of the area (volume) that is affected by the induced stress changes is larger than the ruptured area of the Newcastle fault. Second, the seismic moment magnitude of the 1989 M5.6 Newcastle earthquake is associated with only a fraction of mass removal (1 of 55), following McGarr's mass-moment relationship. Lastly, these findings confirm ongoing seismicity in the Newcastle region since the beginning of the 19th century after a dormant period of 10,000 years of no seismicity.

  13. Motivational Factors Underlying Problem Solving: Comparing Wolf and Dog Puppies' Explorative and Neophobic Behaviors at 5, 6, and 8 Weeks of Age.

    PubMed

    Marshall-Pescini, Sarah; Virányi, Zsófia; Kubinyi, Enikő; Range, Friederike

    2017-01-01

    Background: Wolves have been shown to be better in independent problem-solving tasks than dogs, however it is unclear whether cognitive or motivational factors underlie such differences. In a number of species problem solving has been linked to both persistence in exploration and neophobia, suggesting both these aspects may underlie dog-wolf differences in problem solving. Indeed adult wolves have been shown to be more likely to approach a novel object and more persistent in their investigation of it, but also slower in making contact with it and more fearful of it than dogs. Methods: In the current study we investigated potential differences in equally-raised dogs' and wolves' explorative and neophobic behaviors in a novel environment and with novel objects at 5, 6, and 8 weeks of age. Results: Results showed that wolves were more persistent in exploring both the environment and the objects than dogs, and this was the case at all ages. There were no differences in the frequency of fear-related behaviors and time spent in proximity to humans. Stress-related behaviors were similarly expressed at 5 and 6 weeks, although wolves showed a higher frequency of such behaviors at 8 weeks. Discussion: Overall, results with puppies confirm those with adult animals: wolves appear to be more explorative than dogs. Such motivational differences need to be taken into account when comparing dogs and wolves in cognitive tasks.

  14. Motivational Factors Underlying Problem Solving: Comparing Wolf and Dog Puppies' Explorative and Neophobic Behaviors at 5, 6, and 8 Weeks of Age

    PubMed Central

    Marshall-Pescini, Sarah; Virányi, Zsófia; Kubinyi, Enikő; Range, Friederike

    2017-01-01

    Background: Wolves have been shown to be better in independent problem-solving tasks than dogs, however it is unclear whether cognitive or motivational factors underlie such differences. In a number of species problem solving has been linked to both persistence in exploration and neophobia, suggesting both these aspects may underlie dog-wolf differences in problem solving. Indeed adult wolves have been shown to be more likely to approach a novel object and more persistent in their investigation of it, but also slower in making contact with it and more fearful of it than dogs. Methods: In the current study we investigated potential differences in equally-raised dogs' and wolves' explorative and neophobic behaviors in a novel environment and with novel objects at 5, 6, and 8 weeks of age. Results: Results showed that wolves were more persistent in exploring both the environment and the objects than dogs, and this was the case at all ages. There were no differences in the frequency of fear-related behaviors and time spent in proximity to humans. Stress-related behaviors were similarly expressed at 5 and 6 weeks, although wolves showed a higher frequency of such behaviors at 8 weeks. Discussion: Overall, results with puppies confirm those with adult animals: wolves appear to be more explorative than dogs. Such motivational differences need to be taken into account when comparing dogs and wolves in cognitive tasks. PMID:28232814

  15. Small mammal utilization by Middle Stone Age humans at Die Kelders Cave 1 and Pinnacle Point Site 5-6, Western Cape Province, South Africa.

    PubMed

    Armstrong, Aaron

    2016-12-01

    Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations. Based on comparisons with control assemblages of known accumulation, it is evident that humans accumulated many of the Cape dune mole-rats, hares, and size 1 bovids at DK1. The patterning of cut-marked and burned mole-rat remains at DK1 provides evidence in the MSA for the systematic utilization of small mammals for their skins and as a protein source. Unlike DK1, small mammals and size 1 bovids constitute only a small portion of the PP5-6 mammals and they exhibit little evidence of human accumulation. Nocturnal and diurnal raptors accumulated most of the small fauna at PP5-6. The nominal presence of small mammals in the PP5-6 fauna is atypical of MSA sites in the Cape Floristic Region, where they are abundant and often constitute large portions of MSA archaeofaunas. DK1 humans maximized the environmental yield by exploiting low-quality resources, a strategy employed possibly in response to localized environmental conditions and to greater human population densities. In comparison, the MIS5-4 humans at PP5-6 did not exploit small mammals and instead focused on higher-quality resources like shellfish and large ungulates. Humans and predators accumulated few small mammals at PP5-6, suggesting that these taxa may have been less abundant near the site and/or that humans could afford to concentrate on high-quality resources, perhaps because of a higher-yield local environment. This study suggests that an adaptive response to the environmental conditions of MIS4 was

  16. Alkali therapy attenuates the progression of kidney injury via Na/H exchanger inhibition in 5/6 nephrectomized rats.

    PubMed

    Kim, Sejoong; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Han, Jin Suk

    2014-05-01

    Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

  17. Histopathological characterization of renal tubular and interstitial changes in 5/6 nephrectomized marmoset monkeys (Callithrix jacchus).

    PubMed

    Suzuki, Yui; Yamaguchi, Itaru; Myojo, Kensuke; Kimoto, Naoya; Imaizumi, Minami; Takada, Chie; Sanada, Hiroko; Takaba, Katsumi; Yamate, Jyoji

    2015-01-01

    Common marmosets (Callithrix jacchus) have become a useful animal model, particularly for development of biopharmaceuticals. While various renal failure models have been established in rodents, there is currently no acceptable model in marmosets. We analyzed the damaged renal tubules and tubulointerstitial changes (inflammation and fibrosis) of 5/6 nephrectomized (Nx) common marmosets by histopathological/immunohistochemical methods, and compared these findings to those in 5/6 Nx SD rats. In Nx marmosets and rats sacrificed at 5 and 13 weeks after Nx, variously dilated and atrophied renal tubules were seen in the cortex in common; however, the epithelial proliferating activity was much less in Nx marmosets. Furthermore, the degrees of inflammation and fibrosis seen in the affected cortex were more severe and massive in Nx marmosets with time-dependent increase. Interestingly, inflammation in Nx marmosets, of which degree was less in Nx rats, consisted of a large number of CD3-positive T cells and CD20-positive B cells (occasionally forming follicles), and a few CD68-positive macrophages. Based on these findings, lymphocytes might contribute to the progressive renal lesions in Nx marmosets. Fibrotic areas in Nx marmosets comprised myofibroblasts expressing vimentin and α-smooth muscle actin (α-SMA), whereas along with vimentin and α-SMA expressions, desmin was expressed in myofibroblasts in Nx rats. This study shows that there are some differences in renal lesions induced by Nx between marmosets and rats, which would provide useful, base-line information for pharmacology and toxicology studies using Nx marmosets.

  18. 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…

  19. 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.…

  20. EVALUATION OF IMMUNOASSAY METHODS FOR DETERMINATION OF 3,5,6-TRICHLORO-2-PYRIDINOL IN MULTIPLE SAMPLE MEDIA

    EPA Science Inventory

    Two enzyme-linked immunosorbent assay (ELISA) methods were evaluated for the determination of 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) in multiple sample media (dust, soil, food, and urine). The dust and soil samples were analyzed by the RaPID (TM) commercial immunoassay testing ...

  1. 17 CFR 5.6 - Maintenance of minimum financial requirements by retail foreign exchange dealers and futures...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... engaging in retail forex transactions. 5.6 Section 5.6 Commodity and Securities Exchanges COMMODITY FUTURES... forex transactions. (a) Each futures commission merchant offering or engaging in retail forex... engage in retail forex transactions and each person registered as a retail foreign exchange dealer or...

  2. 17 CFR 5.6 - Maintenance of minimum financial requirements by retail foreign exchange dealers and futures...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... engaging in retail forex transactions. 5.6 Section 5.6 Commodity and Securities Exchanges COMMODITY FUTURES... forex transactions. (a) Each futures commission merchant offering or engaging in retail forex... engage in retail forex transactions and each person registered as a retail foreign exchange dealer or...

  3. 17 CFR 5.6 - Maintenance of minimum financial requirements by retail foreign exchange dealers and futures...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... engaging in retail forex transactions. 5.6 Section 5.6 Commodity and Securities Exchanges COMMODITY FUTURES... forex transactions. (a) Each futures commission merchant offering or engaging in retail forex... engage in retail forex transactions and each person registered as a retail foreign exchange dealer or...

  4. 17 CFR 5.6 - Maintenance of minimum financial requirements by retail foreign exchange dealers and futures...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... engaging in retail forex transactions. 5.6 Section 5.6 Commodity and Securities Exchanges COMMODITY FUTURES... forex transactions. (a) Each futures commission merchant offering or engaging in retail forex... engage in retail forex transactions and each person registered as a retail foreign exchange dealer or...

  5. 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.

  6. Nifty Alleles, a Plethora of Interactions, and Imagination Advance Understanding of Smc5/6's Roles with Chromosomes.

    PubMed

    Langston, Rachel E; Weinert, Ted

    2015-12-17

    The Smc5/6 complex is involved in DNA replication and repair, but why it is essential is less clear. In this issue of Molecular Cell, Menolfi et al. (2015) use cell cycle-specific alleles to link the essential function of Smc5/6 to resolving replication problems that persist into G2.

  7. Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites.

    PubMed

    Židková, Monika; Linhart, Igor; Balíková, Marie; Himl, Michal; Váňa, Lubomír; Vetýška, Michal; Páleníček, Tomáš; Lhotková, Eva; Dušek, Martin

    2016-07-12

    1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.

  8. Ultrafast excited state dynamics of 5,6-dihydroxyindole, a key eumelanin building block: nonradiative decay mechanism.

    PubMed

    Gauden, Magdalena; Pezzella, Alessandro; Panzella, Lucia; Napolitano, Alessandra; d'Ischia, Marco; Sundström, Villy

    2009-09-17

    As part of a program designed to elucidate the excited state properties of key eumelanin building blocks, we report herein a study of 5,6-dihydroxyindole (DHI) in phosphate buffer at pH 3 and pH 7 using femtosecond transient absorption spectroscopy. The transient absorption changes following excitation at 266 nm were used to directly monitor relaxation of the excited states. It was found that the initially generated excited state of DHI, exhibiting two main absorption bands at approximately 450 and approximately 550 nm, decays with a time constant of 5-10 ps to the equilibrated singlet excited state characterized by a very similar spectrum. This latter state then decays to the ground state and the triplet state with a characteristic time of approximately 140-180 ps. Concomitant with the singlet excited state decay of DHI, spectral features characteristic of the DHI cation radical (band at approximately 575 nm) and the triplet state (band at 440-450 nm) are detected. These species do not decay further since geminate recombination of the solvated electron and the DHI radical cation, as well as deprotonation of the cation to form the neutral semiquinone radical, occur on a time scale longer than that covered by the present experiments. These results offer novel insights into the mechanisms of nonradiative decay of eumelanin building blocks of possible relevance to the putative photoprotective and phototoxic roles of these biopolymers.

  9. Rooted in Time. Weymouth Woods-Sandhills Nature Preserve: An Environmental Education Designed for Grades 5-6.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Environment, Health, and Natural Resources, Raleigh. Div. of Parks and Recreation.

    This curriculum guide was developed to provide environmental education through a series of hands-on activities for the classroom and the outdoor setting of Weymouth Woods-Sandhills Nature Preserve, North Carolina. This activity packet, designed for grades 5 and 6, meets established curriculum objectives of the North Carolina Department of Public…

  10. 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.…

  11. 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…

  12. 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,…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. Photophysical Properties of a 1,2,3,4,5,6-Hexasubstituted Fullerene Derivative

    PubMed Central

    Chin, Khin K.; Chuang, Shih-Ching; Hernandez, Billy; Selke, Matthias; Foote, Christopher S.

    2008-01-01

    The photophysical properties of a novel 1,2,3,4,5,6-hexasusbstituted fullerene derivative (1) are examined in this study. In addition to the ground state absorption spectrum of 1 we report its triplet-triplet absorption spectrum and molar extinction coefficient (ΔεT-T), as well as the triplet quantum yield (ΦT), lifetime (τT), and energy (ET). The saturation of a single six-member ring on the fullerene cage results in significant changes in the triplet state properties as compared to that of pristine C60. The triplet-triplet absorption spectrum shows a hypsochromic shift in long wavelength absorption and both the triplet state lifetime and triplet quantum yield are decreased. The triplet energy was found to be similar to that of C60. In addition, the quantum yield (ΦΔ) of singlet oxygen generated by 1 was calculated and is found to be significantly less than in the case of C60. PMID:17181318

  1. The preparation and biological activity of methyl 5,6-epoxy-retinoate

    PubMed Central

    Morgan, B.; Thompson, J. N.

    1966-01-01

    1. Oxidation of methyl retinoate with monoperphthalic acid gave methyl 5,6-epoxyretinoate, obtained as pale-yellow crystals, m.p. 89°. 2. The structure of the epoxide was confirmed by its ultraviolet, infrared, nuclear-magnetic-resonance and mass spectra. 3. The biological properties of the epoxide were investigated in male and female rats, and were found to be qualitatively similar to those of retinoic acid and methyl retinoate. 4. When administered to male rats reared on a vitamin A-free diet, the epoxide permitted growth although it did not maintain good general health. 5. Rats given a vitamin A-free diet and supplements of the epoxide had degenerate testes. 6. Female rats, maintained on a vitamin A-free diet containing retinoic acid and given supplements of the epoxide during pregnancy, resorbed their foetuses and failed to deliver litters. 7. The threshold of the electroretinogram response in male rats reared on a vitamin A-free diet with supplements of the epoxide was elevated above normal and was similar to that of rats maintained with methyl retinoate. 8. The oral administration of the epoxy acid to rats did not result in the accumulation of the corresponding epoxy alcohol in their livers. PMID:16742464

  2. Pillar[5,6]arene-functionalized silicon dioxide: synthesis, characterization, and adsorption of herbicide.

    PubMed

    Zhou, Ting; Song, Nan; Yu, Hao; Yang, Ying-Wei

    2015-02-03

    A layer of synthetic supramolecular macrocycles, that is, perhydroxyl-pillar[5]arene and perhydroxyl-pillar[6]arene, has been covalently attached to hydrophilic silica supports through Si-O-Si linkages with a coverage of up to 250 μmol pillar[5,6]arenes/g to form novel absorbent hybrid materials. Their adsorption toward a typical herbicide, namely, paraquat, from its aqueous solution has been investigated. Kinetic studies disclosed that paraquat adsorption fits a first-order kinetic model. Equilibrium adsorption data could be explained very well by the Langmuir equation. The pillar[6]arene-modified materials showed more obvious adsorption as compared with pillar[5]arene-modified ones and the saturation adsorption quantity reached about 0.20 mmol of paraquat per gram of materials. The entire process of adsorption was endothermic, and significantly an elevated temperature led to an increase in the adsorption quantity. This new type of pillarene-based adsorbent materials can be considered as a potential adsorbent for harmful substances removal from wastewaters.

  3. DNA binding studies of 3, 5, 6-trichloro-2-pyridinol pesticide metabolite.

    PubMed

    Kashanian, Soheila; Shariati, Zohreh; Roshanfekr, Hamideh; Ghobadi, Sirous

    2012-07-01

    3, 5, 6-Trichloro-2-pyridinol (TCP) is a stable metabolite of two major pesticides, Chlopyrifos insecticide and Triclopyr herbicide, which are widely used in the world. The potential health hazard associated with TCP is identified due to its high affinity to the DNA molecule. Therefore, in this study, the interaction of native calf thymus DNA with TCP has been investigated using spectrophotometric, circular dichroism (CD), spectrofluorometric, viscometric and voltametric techniques. It was found that TCP molecules could interact with DNA via a groove-binding mode, as evidenced by hyperchromism, with no red shift in the UV absorption band of TCP, no changes in K(b) values in the presence of salt, no significant changes in the specific viscosity and CD spectra of DNA, and a decrease in peak currents with no shift in the voltamogram. In addition, TCP is able to release Hoechst 33258, a strong groove binder, in the DNA solutions. The results are indicative of the groove-binding mode of TCP to DNA.

  4. Expression of Spgatae, the Strongylocentrotus purpuratus ortholog of vertebrate GATA4/5/6 factors.

    PubMed

    Lee, Pei Yun; Davidson, Eric H

    2004-12-01

    Spgatae is the sea urchin ortholog of the vertebrate gata4/5/6 genes, as confirmed by phylogenetic analysis. The accumulation of Spgatae transcripts during embryonic development and the spatial pattern of expression are reported here. Expression was first detected in the 15 h blastula. The number of Spgatae RNA molecules increases steadily during blastula stages, with expression peaking during gastrulation. After gastrulation is complete, the level of expression decreases until the end of embryogenesis. Whole mount in situ hybridization showed that Spgatae transcripts were first detected in a ring of prospective mesoderm cells in the vegetal plate. Spgatae expression then expands to include the entire vegetal plate at the mesenchyme blastula stage. During gastrulation Spgatae is expressed at the blastopore, and at prism stage strongly in the hindgut and midgut but not foregut, and also in mesoderm cells at the tip of the archenteron. Towards the end of embryogenesis, expression in the hindgut decreases. The terminal pattern of expression is in midgut plus coelomic pouches.

  5. Effects of the May 5-6, 1973, storm in the Greater Denver area, Colorado

    USGS Publications Warehouse

    Hansen, Wallace R.

    1973-01-01

    Rain began falling on the Greater Denver area the evening of Saturday, May 5, 1973, and continued through most of Sunday, May 6. Below about 7,000 feet altitude, the precipitation was mostly rain; above that altitude, it was mostly snow. Although the rate of fall was moderate, at least 4 inches of rain or as much as 4 feet of snow accumulated in some places. Sustained precipitation falling at a moderate rate thoroughly saturated the ground and by midday Sunday sent most of the smaller streams into flood stage. The South Platte River and its major tributaries began to flood by late Sunday evening and early Monday morning. Geologic and hydrologic processes activated by the May 5-6 storm caused extensive damage to lands and to manmade structures in the Greater Denver area. Damage was generally most intense in areas where man had modified the landscape--by channel constrictions, paving, stripping of vegetation and topsoil, and oversteepening of hillslopes. Roads, bridges, culverts, dams, canals, and the like were damaged or destroyed by erosion and sedimentation. Streambanks and structures along them were scoured. Thousands of acres of croplands, pasture, and developed urban lands were coated with mud and sand. Flooding was intensified by inadequate storm sewers, blocked drains, and obstructed drainage courses. Saturation of hillslopes along the Front Range caused rockfalls, landslides, and mudflows as far west as Berthoud Pass. Greater attention to geologic conditions in land-use planning, design, and construction would minimize storm damage in the future.

  6. 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…

  7. 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…

  8. 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);…

  9. 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…

  10. 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.

  11. Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance

    PubMed Central

    Menolfi, Demis; Delamarre, Axel; Lengronne, Armelle; Pasero, Philippe; Branzei, Dana

    2015-01-01

    Summary The essential functions of the conserved Smc5/6 complex remain elusive. To uncover its roles in genome maintenance, we established Saccharomyces cerevisiae cell-cycle-regulated alleles that enable restriction of Smc5/6 components to S or G2/M. Unexpectedly, the essential functions of Smc5/6 segregated fully and selectively to G2/M. Genetic screens that became possible with generated alleles identified processes that crucially rely on Smc5/6 specifically in G2/M: metabolism of DNA recombination structures triggered by endogenous replication stress, and replication through natural pausing sites located in late-replicating regions. In the first process, Smc5/6 modulates remodeling of recombination intermediates, cooperating with dissolution activities. In the second, Smc5/6 prevents chromosome fragility and toxic recombination instigated by prolonged pausing and the fork protection complex, Tof1-Csm3. Our results thus dissect Smc5/6 essential roles and reveal that combined defects in DNA damage tolerance and pausing site-replication cause recombination-mediated DNA lesions, which we propose to drive developmental and cancer-prone disorders. PMID:26698660

  12. Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE.

    PubMed

    Moradi-Fard, Sarah; Sarthi, Jessica; Tittel-Elmer, Mireille; Lalonde, Maxime; Cusanelli, Emilio; Chartrand, Pascal; Cobb, Jennifer A

    2016-08-01

    SMC proteins constitute the core members of the Smc5/6, cohesin and condensin complexes. We demonstrate that Smc5/6 is present at telomeres throughout the cell cycle and its association with chromosome ends is dependent on Nse3, a subcomponent of the complex. Cells harboring a temperature sensitive mutant, nse3-1, are defective in Smc5/6 localization to telomeres and have slightly shorter telomeres. Nse3 interacts physically and genetically with two Rap1-binding factors, Rif2 and Sir4. Reduction in telomere-associated Smc5/6 leads to defects in telomere clustering, dispersion of the silencing factor, Sir4, and a loss in transcriptional repression for sub-telomeric genes and non-coding telomeric repeat-containing RNA (TERRA). SIR4 recovery at telomeres is reduced in cells lacking Smc5/6 functionality and vice versa. However, nse3-1/ sir4 Δ double mutants show additive defects for telomere shortening and TPE indicating the contribution of Smc5/6 to telomere homeostasis is only in partial overlap with SIR factor silencing. These findings support a role for Smc5/6 in telomere maintenance that is separate from its canonical role(s) in HR-mediated events during replication and telomere elongation.

  13. Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE

    PubMed Central

    Chartrand, Pascal; Cobb, Jennifer A.

    2016-01-01

    SMC proteins constitute the core members of the Smc5/6, cohesin and condensin complexes. We demonstrate that Smc5/6 is present at telomeres throughout the cell cycle and its association with chromosome ends is dependent on Nse3, a subcomponent of the complex. Cells harboring a temperature sensitive mutant, nse3-1, are defective in Smc5/6 localization to telomeres and have slightly shorter telomeres. Nse3 interacts physically and genetically with two Rap1-binding factors, Rif2 and Sir4. Reduction in telomere-associated Smc5/6 leads to defects in telomere clustering, dispersion of the silencing factor, Sir4, and a loss in transcriptional repression for sub-telomeric genes and non-coding telomeric repeat-containing RNA (TERRA). SIR4 recovery at telomeres is reduced in cells lacking Smc5/6 functionality and vice versa. However, nse3-1/ sir4 Δ double mutants show additive defects for telomere shortening and TPE indicating the contribution of Smc5/6 to telomere homeostasis is only in partial overlap with SIR factor silencing. These findings support a role for Smc5/6 in telomere maintenance that is separate from its canonical role(s) in HR-mediated events during replication and telomere elongation. PMID:27564449

  14. Non-SMC Element 2 (NSMCE2) of the SMC5/6 Complex Helps to Resolve Topological Stress

    PubMed Central

    Verver, Dideke E.; Zheng, Yi; Speijer, Dave; Hoebe, Ron; Dekker, Henk L.; Repping, Sjoerd; Stap, Jan; Hamer, Geert

    2016-01-01

    The structural maintenance of chromosomes (SMC) protein complexes shape and regulate the structure and dynamics of chromatin, thereby controlling many chromosome-based processes such as cell cycle progression, differentiation, gene transcription and DNA repair. The SMC5/6 complex is previously described to promote DNA double-strand breaks (DSBs) repair by sister chromatid recombination, and found to be essential for resolving recombination intermediates during meiotic recombination. Moreover, in budding yeast, SMC5/6 provides structural organization and topological stress relief during replication in mitotically dividing cells. Despite the essential nature of the SMC5/6 complex, the versatile mechanisms by which SMC5/6 functions and its molecular regulation in mammalian cells remain poorly understood. By using a human osteosarcoma cell line (U2OS), we show that after the CRISPR-Cas9-mediated removal of the SMC5/6 subunit NSMCE2, treatment with the topoisomerase II inhibitor etoposide triggered an increased sensitivity in cells lacking NSMCE2. In contrast, NSMCE2 appeared not essential for a proper DNA damage response or cell survival after DSB induction by ionizing irradiation (IR). Interestingly, by way of immunoprecipitations (IPs) and mass spectrometry, we found that the SMC5/6 complex physically interacts with the DNA topoisomerase II α (TOP2A). We therefore propose that the SMC5/6 complex functions in resolving TOP2A-mediated DSB-repair intermediates generated during replication. PMID:27792189

  15. 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.

  16. Advanced Gas Reactor (AGR)-5/6/7 Fuel Irradiation Experiments in the Advanced Test Reactor

    SciTech Connect

    A. Joseph Palmer; David A. Petti; S. Blaine Grover

    2014-04-01

    The United States Department of Energy’s Very High Temperature Reactor (VHTR) Advanced Gas Reactor (AGR) Fuel Development and Qualification Program will be irradiating up to seven separate low enriched uranium (LEU) tri-isotopic (TRISO) particle fuel (in compact form) experiments in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). These irradiations and fuel development are being accomplished to support development of the next generation reactors in the United States. The goals of the irradiation experiments are to provide irradiation performance data to support fuel process development, to qualify fuel for normal operating conditions, to support development and validation of fuel performance and fission product transport models and codes, and to provide irradiated fuel and materials for post irradiation examination (PIE) and safety testing. The experiments, which each consist of at least five separate capsules, are being irradiated in an inert sweep gas atmosphere with individual on-line temperature monitoring and control of each capsule. The sweep gases also have on-line fission product monitoring the effluent from each capsule to track performance of the fuel during irradiation. The first two experiments (designated AGR-1 and AGR-2), have been completed. The third and fourth experiments have been combined into a single experiment designated AGR-3/4, which started its irradiation in December 2011 and is currently scheduled to be completed in April 2014. The design of the fuel qualification experiment, designated AGR-5/6/7, is well underway and incorporates lessons learned from the three previous experiments. Various design issues will be discussed with particular details related to selection of thermometry.

  17. 2,5,6,9,10-Pentabromocyclododecanols (PBCDOHs): a new class of HBCD transformation products.

    PubMed

    Heeb, Norbert V; Zindel, Daniel; Schweizer, W Bernd; Lienemann, Peter

    2012-07-01

    Pentabromocyclododecanols (PBCDOHs) are potential environmental transformation products of hexabromocyclododecanes (HBCDs). They are also potential stage one metabolites of biological HBCD transformations. Herein, we present analytical evidence that PBCDOHs are also constituents of technical HBCDs and flame-proofed polystyrenes (FP-PSs). PBCDOHs are possibly formed during the synthesis of technical HBCD, presumably during the bromination of cyclododecatrienes in aqueous isobutanol together with isobutoxypentabromocyclododecanes (iBPBCDs), which have been identified in these materials recently. Of the 64 stereoisomers possible, eight pairs of enantiomers, named α-, β-, γ-, δ-, ε-, ζ-, η-, and θ-PBCDOHs were separated with a combination of normal-, reversed- and chiral-phase LC. Crystal structure analysis revealed the stereochemistry of the α-PBCDOH pair of enantiomers, which was assigned to (1S,2S,5R,6S,9S,10R)-2,5,6,9,10-pentabromocyclododecanol and its enantiomer. Mass spectrometric data are in accordance with the expected isotope patterns. On a C(18)-RP-column, the polar PBCDOHs eluted before the HBCD and iBPBCD classes of compounds. PBCDOHs were also found in FP-PS materials. The stereoisomer patterns varied considerably in these materials like those of HBCDs and iBPBCDs. Expanded polystyrenes were rich in late-eluting stereoisomers, similar to technical HBCD mixtures. Extruded polystyrenes contained more of the polar, faster-eluting isomers. The presented chromatographic and analytical methods allow a stereoisomer-specific search for PBCDOHs in biota samples, which might have experienced metabolic HBCD transformation reactions. Besides this potential source, it has to be recognized that PBCDOHs are by-products in technical HBCDs and in flame-proofed polystyrenes. Therefore, it is likely that PBCDOHs and iBPBCDs are released to the environment together with HBCD-containing plastic materials.

  18. 5-(4-Chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivatives as lipophilic cyclic analogues of baclofen: design, synthesis, and neuropharmacological evaluation.

    PubMed

    Abdel-Hafez, Atef A; Abdel-Wahab, Basel A

    2008-09-01

    In trials to preserve the pharmacological profile and improve the bioavailability via lipophilicity increment of baclofen 1 and searching for more potent and less toxic muscle relaxants and analgesics, nine substituted cyclic analogues of 1 were designed and synthesized. The target derivatives 5-(4-chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one (11-19) were obtained through amide formation to the corresponding intermediates (2-10) followed by cyclization using acetic anhydride. The structures of the target compounds (11-19) were confirmed by IR, (1)H NMR, MS, and elemental analyses. The neuropharmacological activities of these lipophilic cyclic analogues (11-19) were assessed for their effects on motor activity, muscle relaxation, pain relief and impaired cognition, by intraperitoneal administration at a dose of 3mg/kg with reference to those of baclofen 1. Our results showed that compounds 11-14 are devoid of all of the tested pharmacological effects associated with 1. In all paradigms tested, undecyl, tridecyl, heptdec-8-enyl and benzyl substituted analogue derivatives (15, 16, 18, and 19) revealed a significant neurological activity being vividly favorable comparable with baclofen 1. 2-Benzyl-5-(4-chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivative 19 is the most active candidate with high significant neurological potencies, while 5-(4-chlorophenyl)-2-(dec-8-enyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivative 17 displayed activity at relatively higher time interval. These results probe a new structurally distinct class incorporating 1,3-oxazepine nucleus as promising candidates as GABA(B) agonists for further investigations.

  19. 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…

  20. 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:…

  1. 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…

  2. 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…

  3. 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…

  4. 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.

  5. Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics.

    PubMed

    Aparicio-Trejo, Omar Emiliano; Tapia, Edilia; Molina-Jijón, Eduardo; Medina-Campos, Omar Noel; Macías-Ruvalcaba, Norma Angélica; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; García-Arroyo, Fernando E; Cristóbal, Magdalena; Sánchez-Lozada, Laura Gabriela; Pedraza-Chaverri, José

    2016-11-01

    Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts. In addition, it was found that 5/6NX shifted mitochondrial dynamics to fusion, which was evidenced by increased optic atrophy 1 and mitofusin 1 (Mfn1) and decreased fission 1 and dynamin-related protein 1 expressions. These data were confirmed by morphological analysis and immunoelectron microscopy of Mfn-1. All the above-described mechanisms were prevented by curcumin. Also, it was found that curcumin prevented renal dysfunction by improving renal blood flow and the total antioxidant capacity induced by 5/6NX. Moreover, in glomeruli and proximal tubules 5/6NX-induced superoxide anion production by uncoupled nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent way, this latter was associated with increased phosphorylation of serine 304 of p47phox subunit of NOX. In conclusion, this study shows that curcumin pretreatment decreases early 5/6NX-induced altered mitochondrial dynamics, bioenergetics, and oxidative stress, which may be associated with the preservation of renal function. © 2016 BioFactors, 00(00):000000, 2016.

  6. Application of Subspace Detection to the 6 November 2011 M5.6 Prague, Oklahoma Aftershock Sequence

    NASA Astrophysics Data System (ADS)

    McMahon, N. D.; Benz, H.; Johnson, C. E.; Aster, R. C.; McNamara, D. E.

    2015-12-01

    Subspace detection is a powerful tool for the identification of small seismic events. Subspace detectors improve upon single-event matched filtering techniques by using multiple orthogonal waveform templates whose linear combinations characterize a range of observed signals from previously identified earthquakes. Subspace detectors running on multiple stations can significantly increasing the number of locatable events, lowering the catalog's magnitude of completeness and thus providing extraordinary detail on the kinematics of the aftershock process. The 6 November 2011 M5.6 earthquake near Prague, Oklahoma is the largest earthquake instrumentally recorded in Oklahoma history and the largest earthquake resultant from deep wastewater injection. A M4.8 foreshock on 5 November 2011 and the M5.6 mainshock triggered tens of thousands of detectable aftershocks along a 20 km splay of the Wilzetta Fault Zone known as the Meeker-Prague fault. In response to this unprecedented earthquake, 21 temporary seismic stations were deployed surrounding the seismic activity. We utilized a catalog of 767 previously located aftershocks to construct subspace detectors for the 21 temporary and 10 closest permanent seismic stations. Subspace detection identified more than 500,000 new arrival-time observations, which associated into more than 20,000 locatable earthquakes. The associated earthquakes were relocated using the Bayesloc multiple-event locator, resulting in ~7,000 earthquakes with hypocentral uncertainties of less than 500 m. The relocated seismicity provides unique insight into the spatio-temporal evolution of the aftershock sequence along the Wilzetta Fault Zone and its associated structures. We find that the crystalline basement and overlying sedimentary Arbuckle formation accommodate the majority of aftershocks. While we observe aftershocks along the entire 20 km length of the Meeker-Prague fault, the vast majority of earthquakes were confined to a 9 km wide by 9 km deep

  7. Rapid and sensitive spectrofluorimetric determination of enrofloxacin, levofloxacin and ofloxacin with 2,3,5,6-tetrachloro- p-benzoquinone

    NASA Astrophysics Data System (ADS)

    Ulu, Sevgi Tatar

    2009-06-01

    A highly sensitive spectrofluorimetric method was developed for the first time, for the analysis of three fluoroquinolones (FQ) antibacterials, namely enrofloxacin (ENR), levofloxacin (LEV) and ofloxacin (OFL) in pharmaceutical preparations through charge transfer (CT) complex formation with 2,3,5,6-tetrachloro- p-benzoquinone (chloranil,CLA). At the optimum reaction conditions, the FQ-CLA complexes showed excitation maxima ranging from 359 to 363 nm and emission maxima ranging from 442 to 488 nm. Rectilinear calibration graphs were obtained in the concentration range of 50-1000, 50-1000 and 25-500 ng mL -1 for ENR, LEV and OFL, respectively. The detection limit was found to be 17 ng mL -1 for ENR, 17 ng mL -1 for LEV, 8 ng mL -1 for OFL, respectively. Excipients used as additive in commercial formulations did not interfere in the analysis. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The proposed method was successfully applied to the analysis of pharmaceutical preparations. The results obtained were in good agreement with those obtained using the official method; no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively.

  8. Toxicity of 3,5,6-trichloro-2-pyridinol tested at multiple stages of zebrafish (Danio rerio) development.

    PubMed

    Suvarchala, Gonuguntla; Philip, Gundala Harold

    2016-08-01

    Organophosphate compounds (OP) are widely used throughout the world for pest control. 3,5,6-Trichloro-2-pyridinol (TCP) is a primary metabolite of two OP compounds namely CP and triclopyr. This study is carried out to know whether a metabolite of parent compound is doing well or harm to biota. The potential effect of TCP was evaluated on development as destabilization of any events transpiring during embryogenesis could be deleterious. To determine this, 4-hpf zebrafish embryos were exposed to five concentrations of TCP (200, 400, 600, 800, 1000 μg/L) or 99.5 % acetone (solvent control). Different early life-stage parameters were observed at four different developmental stages, 24, 48, 72 and 96 hpf. TCP-treated embryo/larvae showed increased mortality, delay in hatching time and decrease in percentage of hatched embryos. Reduction in heartbeat rate, blood flow and body and eye pigmentation was noticed in a dose-dependent manner. Pericardial and yolk sac edema were most severe malformations caused by TCP. Along with this crooked spine/notochord, tail deformation was noticed in hatched and unhatched embryos. The malformations observed provide a good starting point for examination of the molecular mechanisms that are affected during development by TCP. Results gain significance as TCP, which is a breakdown product, appears to be more toxic during development compared to parent compound, CP (our earlier publication).

  9. Phosphorylation regulates proteolytic efficiency of TEV protease detected by a 5(6)-carboxyfluorescein-pyrene based fluorescent sensor.

    PubMed

    He, Yao-Hui; Li, Yan-Mei; Chen, Yong-Xiang

    2016-04-01

    TEV protease is of great importance for in vitro and in vivo site-specific cleavage of proteins. The proteolytic efficiency of TEV protease is often regulated by mutation of the substrate, which is irreversible and hard to be modulated. Herein, a facile and reversible method, based on phosphorylation in the substrate, is developed to regulate the cleavage capability of TEV protease. Phosphorylation at P3 tyrosine hinders the recognition of TEV protease to the substrate by using a robust fluorescent protease sensor. Moreover, the phosphate group can be easily removed by alkaline phosphatases for recovering the proteolytic efficiency of TEV protease. Additionally, 5(6)-carboxyfluorescein and pyrene have been used as high-efficiency mutual fluorophore-quencher pair in the peptide-based protease sensor for the first time, which provides a chance to simultaneously monitor the cleavage process in two respective fluorescence channels. Further studies indicated both dynamic and static components contributing to the mutual quenching system. The phosphorylation-regulated TEV protease proteolysis system can be used in conditional cleavage of protein or peptide tag.

  10. Absolute Locations of Repeating Mw 5.5 - 6.0 Earthquakes on Discovery Transform Fault, EPR

    NASA Astrophysics Data System (ADS)

    Wolfson, M. L.; Boettcher, M. S.; McGuire, J. J.; Collins, J. A.

    2011-12-01

    this study. To compare absolute locations of the repeating events to the high-resolution bathymetric data, it was necessary to perform a relative relocation of the earthquake centroids. We used events from the NOAA hydroacoustic catalog, which have positional accuracies of ~2 km [Fox et al., 2001], to determine accurate absolute locations for the Mw 5.5 - 6.0 events. Initial results show that there are at least 5 distinct rupture patches on Discovery, including the 4 repeating patches found previously, with a mean spacing of 13 km. The repeat time between events in each repeating rupture patch is 5 - 6 years. The relocation technique placed each group within ~7 km of the fault trace. Three of the rupture groups locate on the western segment of Discovery; one on the edge of the lozenge-shaped valley, one in the splay zone, and one near the ITSC. Using the catalog of over 24,000 0≤Mw≤4.6 events recorded during our 2008 ocean bottom seismometer deployment on Discovery, we find that microseismicity on Discovery roughly clusters in the areas between the large-events, suggesting that the frictional properties differ significantly between the large-event rupture patches and the regions of abundant microseismicity.

  11. Roles of phosphate recognition in inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPK1) substrate binding and activation.

    PubMed

    Gosein, Varin; Miller, Gregory J

    2013-09-13

    Inositol phosphate kinases (IPKs) sequentially phosphorylate inositol phosphates (IPs) to yield a group of small signaling molecules involved in diverse cellular processes. IPK1 (inositol 1,3,4,5,6-pentakisphosphate 2-kinase) phosphorylates inositol 1,3,4,5,6-pentakisphosphate to inositol 1,2,3,4,5,6-hexakisphosphate; however, the mechanism of IP recognition employed by IPK1 is currently unresolved. We demonstrated previously that IPK1 possesses an unstable N-terminal lobe in the absence of IP, which led us to propose that the phosphate profile of the IP was linked to stabilization of IPK1. Here, we describe a systematic study to determine the roles of the 1-, 3-, 5-, and 6-phosphate groups of inositol 1,3,4,5,6-pentakisphosphate in IP binding and IPK1 activation. The 5- and 6-phosphate groups were the most important for IP binding to IPK1, and the 1- and 3-phosphate groups were more important for IPK1 activation than the others. Moreover, we demonstrate that there are three critical residues (Arg-130, Lys-170, and Lys-411) necessary for IPK1 activity. Arg-130 is the only substrate-binding N-terminal lobe residue that can render IPK1 inactive; its 1-phosphate is critical for full IPK1 activity and for stabilization of the active conformation of IPK1. Taken together, our results support the model for recognition of the IP substrate by IPK1 in which (i) the 4-, 5-, and 6-phosphates are initially recognized by the C-terminal lobe, and subsequently, (ii) the interaction between the 1-phosphate and Arg-130 stabilizes the N-terminal lobe and activates IPK1. This model of IP recognition, believed to be unique among IPKs, could be exploited for selective inhibition of IPK1 in future studies that investigate the role of higher IPs.

  12. The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and Is Counteracted by the HBV X Protein Shortly after Infection

    PubMed Central

    Daffis, Stephane; Ramakrishnan, Dhivya; Burdette, Dara; Peiser, Leanne; Salas, Eduardo; Ramos, Hilario; Yu, Mei; Cheng, Guofeng; Strubin, Michel; Delaney IV, William E.; Fletcher, Simon P.

    2017-01-01

    The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions. We determined that Smc5/6 localizes with Nuclear Domain 10 (ND10) in PHH. Co-localization has functional implications since depletion of ND10 structural components alters the nuclear distribution of Smc6 and induces HBV gene expression in the absence of HBx. We also found that HBV infection and replication does not induce a prominent global host transcriptional response in PHH, either shortly after infection when Smc5/6 is present, or at later times post-infection when Smc5/6 has been degraded. Notably, HBV and an HBx-negative virus establish high level infection in PHH without inducing expression of interferon-stimulated genes or production of interferons or other cytokines. Our study also revealed that Smc5/6 is degraded in the majority of infected PHH by the time cccDNA transcription could be detected and that HBx RNA is present in cell culture-derived virus preparations as well as HBV patient plasma. Collectively, these data indicate that Smc5/6 is an intrinsic antiviral restriction factor that suppresses HBV transcription when localized to ND10 without inducing a detectable innate immune response. Our data also suggest that HBx protein may be initially expressed by delivery of extracellular HBx RNA into HBV-infected cells. PMID:28095508

  13. Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy.

    PubMed

    Marchesi, Chiara; Essalmani, Rachid; Lemarié, Catherine A; Leibovitz, Eyal; Ebrahimian, Talin; Paradis, Pierre; Seidah, Nabil G; Schiffrin, Ernesto L; Prat, Annik

    2011-11-01

    Proprotein convertase (PC) 5/6 belongs to a family of secretory proteases involved in proprotein proteolysis. Several studies suggest a role for PC5/6 in cardiovascular disease. Because lethality at birth of mice lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 (pcsk5) is specifically inactivated in endothelial cells (ecKO), which are viable and do not exhibit overt abnormalities. In order to uncover the function of PC5/6 in the cardiovascular system, the effect of ecKO was studied in aging mice. In 16 to 18-month-old ecKO mice, the left ventricle (LV) mass, media cross-sectional area of aorta and coronary arteries, and media-to-lumen ratio of mesenteric arteries were decreased. The LV presented decreased diastolic function, and mesenteric arteries showed decreased stiffness. Collagen was decreased in the LV myocardial interstitium and perivascularly in coronary arteries and aorta. Cardiovascular hypotrophy likely develops with aging, since no significant changes were observed in 2-month-old ecKO mice. Fibroblasts, as a source of collagen in myocardium and vasculature, may play a role in the decrease in collagen deposition. Fibroblasts co-cultured with ecKO endothelial cells showed decreased collagen production, decreased insulin-like growth factor (IGF)-1/Akt/mTOR signaling, and enhanced autophagic activation. PC5/6 inactivation in endothelial cells results in cardiovascular hypotrophy associated with decreased collagen deposition, decreased LV diastolic function, and vascular stiffness, suggesting a trophic role of endothelial PC5/6 in the cardiovascular system, likely mediated by IGF-1/Akt/mTOR signaling and control of autophagy.

  14. 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.

  15. 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…

  16. In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate

    PubMed Central

    Essalmani, Rachid; Zaid, Ahmed; Marcinkiewicz, Jadwiga; Chamberland, Ann; Pasquato, Antonella; Seidah, Nabil G.; Prat, Annik

    2008-01-01

    The proprotein convertase PC5/6 cleaves protein precursors after basic amino acids and is essential for implantation in CD1/129/Sv/C57BL/6 mixed-background mice. Conditional inactivation of Pcsk5 in the epiblast but not in the extraembryonic tissue bypassed early embryonic lethality but resulted in death at birth. PC5/6-deficient embryos exhibited Gdf11-related phenotypes such as altered anteroposterior patterning with extra vertebrae and lack of tail and kidney agenesis. They also exhibited Gdf11-independent phenotypes, such as a smaller size, multiple hemorrhages, collapsed alveoli, and retarded ossification. In situ hybridization revealed overlapping PC5/6 and Gdf11 mRNA expression patterns. In vitro and ex vivo analyses showed that the selectivity of PC5/6 for Gdf11 essentially resides in the presence of a P1′ Asn in the RSRR↓N cleavage motif. This work identifies Gdf11 as a likely in vivo specific substrate of PC5/6 and opens the way to the identification of other key substrates of this convertase. PMID:18378898

  17. Repeated cocaine weakens GABAB-Girk signaling in Layer 5/6 pyramidal neurons in the prelimbic cortex

    PubMed Central

    Hearing, Matthew; Kotecki, Lydia; de Velasco, Ezequiel Marron Fernandez; Fajardo-Serrano, Ana; Luján, Rafael; Wickman, Kevin

    2013-01-01

    Summary Repeated cocaine exposure triggers adaptations in Layer 5/6 glutamatergic neurons in the medial prefrontal cortex (mPFC) that promote behavioral sensitization and drug-seeking behavior. While suppression of metabotropic inhibitory signaling has been implicated in these behaviors, underlying mechanisms are unknown. Here, we show that Girk/KIR3 channels mediate most of the GABAB receptor (GABABR)-dependent inhibition of Layer 5/6 pyramidal neurons in the mPFC and that repeated cocaine suppresses this pathway. This adaptation was selective for GABABR-dependent Girk signaling in Layer 5/6 pyramidal neurons of the prelimbic cortex (PrLC) and involved a D1/5 dopamine receptor- and phosphorylation-dependent internalization of GABABR and Girk channels. Persistent suppression of Girk signaling in Layer 5/6 of the dorsal mPFC enhanced cocaine-induced locomotor activity and occluded behavioral sensitization. Thus, the cocaine-induced suppression of GABABR-Girk signaling in Layer 5/6 pyramidal neurons of the prelimbic cortex appears to represent an early adaptation critical for promoting addiction-related behavior. PMID:24094109

  18. 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.

  19. One-pot laccase-catalysed synthesis of 5,6-dihydroxylated benzo[b]furans and catechol derivatives, and their anticancer activity.

    PubMed

    Wellington, Kevin W; Qwebani-Ogunleye, Tozama; Kolesnikova, Natasha I; Brady, Dean; de Koning, Charles B

    2013-04-01

    A commercial laccase, Suberase® from Novozymes, was used to catalyse the synthesis of 5,6-dihydroxylated benzo[b]furans and catechol derivatives. The yields were, in some cases, similar to or better than that obtained by other enzymatic, chemical or electrochemical syntheses. The synthesised derivatives were screened against renal (TK10), melanoma (UACC62), breast (MCF7) and cervical (HeLa) cancer cell lines. GI50, TGI and LC50 are reported for the first time. Anticancer screening showed that the cytostatic effects of the 5,6-dihydroxylated benzo[b]furans were most effective against the melanoma (UACC62) cancer cell line with several compounds exhibiting potent growth inhibitory activities (GI50=0.77-9.76 µM), of which two compounds had better activity than the anticancer agent etoposide (GI50  0.89 µM). One compound exhibited potent activity (GI50=9.73 µM) against the renal (TK10) cancer cell line and two exhibited potent activity (GI50=8.79 and 9.30 µM) against the breast (MCF7) cancer cell line. These results encourage further studies of the 5,6-dihydroxylated benzo[b]furans for their potential application in anticancer therapy.

  20. A novel contrast-induced acute kidney injury model based on the 5/6-nephrectomy rat and nephrotoxicological evaluation of iohexol and iodixanol in vivo.

    PubMed

    Liu, Tong-qiang; Luo, Wei-li; Tan, Xiao; Fang, Yi; Chen, Jing; Zhang, Hui; Yu, Xiao-fang; Cai, Jie-ru; Ding, Xiao-qiang

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.

  1. 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.

  2. Energy and Safety: Science Activities for Elementary Students, Level III (Grades (5-6).

    ERIC Educational Resources Information Center

    Westcott, Dale; And Others

    Thirteen activities are presented that focus on a common phenomenon of a child's world: energy. These activities relate energy, how it occurs, how it is used, and how to use it safely. Each activity includes the purpose, introduction, background, procedure, materials, estimated time for the activity, typical results, safety notes, and more ideas.…

  3. Degeneration of monoamine nerves in anterior byssus retractor muscle of Mytilus induced by 5,6-dihydroxytryptamine.

    PubMed

    Sathananthan, A H

    1976-09-20

    Preliminary ultrastructural studies on the effects of 5,6-Dihydroxytryptamine (5,6-DHT) on the anterior byssus retractor muscle (ABRM) of Mytilus show degeneration of 2 types of monoaminergic nerves after 10 days of drug treatment. One type contained large granular vesicles (560-1,680 A) possibly represent serotonergic and dopaminergic nerves, thought to innervate this muscle. Two other types of profiles seemed to be unaffected by the drug. One conforms to cholinergic nerves while the other has a predominance of large opaque vesicles (1,200-2,500 A). The significance of these findings is discussed in the light of recent observations on the neurotoxic effects of 5,6-DHT on vertebrate and molluscan nerves.

  4. Inhibition of Bovine Viral Diarrhea Virus RNA Synthesis by Thiosemicarbazone Derived from 5,6-Dimethoxy-1-Indanone▿

    PubMed Central

    Castro, Eliana F.; Fabian, Lucas E.; Caputto, María E.; Gagey, Dolores; Finkielsztein, Liliana M.; Moltrasio, Graciela Y.; Moglioni, Albertina G.; Campos, Rodolfo H.; Cavallaro, Lucía V.

    2011-01-01

    In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV). PMID:21430053

  5. Multi-Wavelength Observation Results of the C5.6 Limb Flare of 1 August 2003

    NASA Astrophysics Data System (ADS)

    Li, Hui; You, Jianqi; Du, Qiusheng; Yu, Xingfeng

    2004-11-01

    We obtained a complete set of Hα, Ca Π 8542 Å and He I 10830 Å spectra and slit-jaw Hα images of the C5.6 limb flare of 1 August 2003 using the Multi-channel Infrared Solar Spectrograph (MISS) at Purple Mountain Observatory. This flare was also observed by the Reuven Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) and partially by the Extreme-ultraviolet Imaging Telescope (EIT) on SOHO. This flare underwent a rapid rising and expanding episode in the impulsive phase. All the Hα, Ca Π 8542 Å and He I 10830 Å profiles of the flare are rather wide and the widest profiles were observed in the middle bright part of the flare instead of at the flare loop top near the flare maximum. The flare manifested obvious rotation in the flare loop and the decrease of the rotation angular speed with time at the loop-top may imply a de-twisting process of the magnetic field. The significant increases of the Doppler widths of these lines in the impulsive phase reflect quick heating of the chromosphere, and rapid rising and expanding of the flare loop. The RHESSI observations give a thermal energy spectrum for this flare, and two thermal sources and no non-thermal source are found in the reconstructed RHESSI images. This presumably indicates that the energy transfer in this flare is mainly by heat conduction. The stronger thermal source is located near the solar limb with its position unchanged in the flare process and spatially coincident with the intense EUV and Hα emissions. The weaker one moved during the flare process and is located in the Hα dark cavities. This flare may support the theory of the magnetic reconnections in the lower solar atmosphere.

  6. Mobile robots II; Proceedings of the Meeting, Cambridge, MA, Nov. 5, 6, 1987

    SciTech Connect

    Wolfe, W.J.; Chun, W.H.

    1988-01-01

    Topics discussed are autonomous vehicle guidance, three-dimensional systems, the Mars rover, motion analysis, and planning and navigation. Particular papers are presented on a real-time system architecture for a mobile robot, distributed scene analysis for autonomous road vehicle guidance, the vision system for a Mars rover, the recovery of motion parameters using optical flow, and Prolog-based world models for mobile robot navigation.

  7. Mesoscale simulations of the November 25-26 and December 5-6 cirrus cases using the RAMS model

    NASA Technical Reports Server (NTRS)

    Harrington, J. L.; Meyers, Michael P.; Cotton, William R.

    1993-01-01

    The Regional Atmospheric Modeling System (RAMS), developed at Colorado State University, was used during the First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment (FIRE) 2 (13 Nov. through 6 Dec. 1991) to provide real time forecasts of cirrus clouds. Forecasts were run once a day, initializing with the 0000 UTC dataset provided by NOAA (Forecast Systems Laboratory (FSL) Mesoscale Analysis and Prediction System (MAPS)). In order to obtain better agreement with observations, a second set of simulations were done for the FIRE 2 cases that occurred on 25-26 Nov. and 5-6 Dec. In this set of simulations, a more complex radiation scheme was used, the Chen/Cotton radiation scheme, along with the nucleation of ice occurring at ice supersaturations as opposed to nucleation occurring at water supersaturations that was done in the actual forecast version. The runs using these more complex schemes took longer wall clock time (7-9 hours for the actual forecasts as compared to 12-14 hrs for the runs using the more complex schemes) however, the final results of the simulations were definitely improved upon. Comparisons between these two sets of simulations are given. Now underway are simulations of these cases using a closed analytical solution for the auto-conversion of ice from a pristine ice class (sizes less than about 50 microns in effective diameter) to a snow class (effective diameters on the order of several hundred microns). This solution is employed along with a new scheme for the nucleation of ice crystals due to Meyers et al and Demott et al. The scheme is derived assuming complete gamma distributions for both the pristine and snow classes. The time rate of change of the number concentration and mass mixing-ratio of each distribution is found by calculating either the flux of crystals that grow beyond a certain critical diameter by vapor deposition in an ice supersaturated regime or by calculating the flux of crystals that evaporate to

  8. Effect of Heating Rate on Densification and Grain Growth During Spark Plasma Sintering of 93W-5.6Ni-1.4Fe Heavy Alloys

    NASA Astrophysics Data System (ADS)

    Hu, Ke; Li, Xiaoqiang; Qu, Shengguan; Li, Yuanyuan

    2013-09-01

    Blended 93W-5.6Ni-1.4Fe powders were sintered via the spark plasma sintering (SPS) technique using heating rates from 10 K min-1 to 380 K min-1 (10 °C min-1 to 380 °C min-1). The kinetics of densification and grain growth were analyzed to identify heating rate effects during the SPS of 93W-5.6Ni-1.4Fe powders. The activation energies for densification were calculated and compared with the experimental values for diffusion and other mass transport phenomena. The results show that for the slowly heated specimens [heating rate <100 K min-1 (100 °C min-1)], densification occurs mainly through dissolution-precipitation of W through the matrix phase and W grain boundary diffusion. The concurrent grain growth is dominated by surface diffusion at a low sintering temperature and by solution-reprecipitation and Ni-enhanced W grain boundary diffusion at a higher temperature. For the specimens sintered with heating rates higher than 100 K min-1 (100 °C min-1), the apparent activation energy value for the mechanism controlling densification is a strong function of the relative density, and fast densification controlled by multiple diffusion mechanisms and intensive viscous flow dominates over the grain growth. High SPS heating rate is favorable to obtain high density and fine-grained tungsten heavy alloys.

  9. Low stress drops observed for M1.5-5.6 Earthquakes During the 2011 Prague, Oklahoma sequence

    NASA Astrophysics Data System (ADS)

    Cochran, E. S.; Sumy, D. F.; Neighbors, C.; Keranen, K. M.

    2015-12-01

    In November 2011, three M≥4.8 earthquakes and thousands of aftershocks occurred along the structurally complex Wilzetta fault system near Prague, Oklahoma. Previous studies suggest that fluid injection in nearby wells was responsible for inducing the M4.8 foreshock [Keranen et al., 2013], which subsequently triggered the M5.6 mainshock [Sumy et al., 2014]. We examine earthquake source properties using waveforms collected by 47 temporary and permanent seismic stations installed within ~100 km of the events. Brune stress drops are calculated for a subset of 278 aftershocks of the Prague, Oklahoma sequence that range in magnitude from M1.0-4.9. We compute the horizontal amplitude spectra and smooth the spectra with a Konno and Ohmachi [1998] filter. We then assume a standard Brune source spectral model and iteratively solve for seismic moment (Mo), corner frequency (fc) and kappa (κ) using a Gauss-Newton method. We are able to recover reasonably fit Mo, fc, and κ for 172 earthquakes, but find the Mo determined by spectra fit are consistently overestimated for events with M<1.5. Therefore only stress drops for the 149 events with initial Mo > 1.5 are reported. The median stress drop is ~0.3 MPa (3 bars), which is significantly lower than typical values (10+ MPa) observed for CEUS events. We find minimal dependence of stress drop on focal depth for the depth range from 1-10 km. However, we observe some spatial variation of stress drops, with higher stress drops observed near the intersection of the mainshock rupture plane with the fault plane associated with the M4.8 aftershock. The low stress drops observed for events on both the foreshock and mainshock fault plane may indicate both of these segments of the Wilzetta fault system were influenced by local wastewater injection. Our results echo those of several recent studies [Hough, 2014; Sun and Hartzell, 2014], which conclude that induced earthquakes have lower stress drops than tectonic events.

  10. Non-Smc element 5 (Nse5) of the Smc5/6 complex interacts with SUMO pathway components.

    PubMed

    Bustard, Denise E; Ball, Lindsay G; Cobb, Jennifer A

    2016-06-15

    The Smc5/6 complex in Saccharomyces cerevisiae contains six essential non-Smc elements, Nse1-6. With the exception of Nse2 (also known as Mms21), which is an E3 small ubiquitin-like modifier (SUMO) ligase, very little is understood about the role of these components or their contribution to Smc5/6 functionality. Our characterization of Nse5 establishes a previously unidentified relationship between the Smc5/6 complex and factors of the SUMO pathway. Nse5 physically associates with the E2 conjugating enzyme, Ubc9, where contacts are stabilized by non-covalent interactions with SUMO. SUMO also mediates the interactions between Nse5 and the two PIAS family E3 SUMO ligases, Siz1 and Siz2. Cells carrying the nse5-ts1 allele or lacking either SIZ1 or SIZ2 exhibit a reduction in Smc5 sumoylation upon MMS treatment and demonstrate functional redundancy for SUMO mediated events in the presence of DNA damage. Overall, given the extensive connection between Nse5 and components of the SUMO pathway, we speculate that one function of the Smc5/6 complex might be as a scaffold center to enable sumoylation events in budding yeast.

  11. Non-Smc element 5 (Nse5) of the Smc5/6 complex interacts with SUMO pathway components

    PubMed Central

    Bustard, Denise E.; Ball, Lindsay G.

    2016-01-01

    ABSTRACT The Smc5/6 complex in Saccharomyces cerevisiae contains six essential non-Smc elements, Nse1-6. With the exception of Nse2 (also known as Mms21), which is an E3 small ubiquitin-like modifier (SUMO) ligase, very little is understood about the role of these components or their contribution to Smc5/6 functionality. Our characterization of Nse5 establishes a previously unidentified relationship between the Smc5/6 complex and factors of the SUMO pathway. Nse5 physically associates with the E2 conjugating enzyme, Ubc9, where contacts are stabilized by non-covalent interactions with SUMO. SUMO also mediates the interactions between Nse5 and the two PIAS family E3 SUMO ligases, Siz1 and Siz2. Cells carrying the nse5-ts1 allele or lacking either SIZ1 or SIZ2 exhibit a reduction in Smc5 sumoylation upon MMS treatment and demonstrate functional redundancy for SUMO mediated events in the presence of DNA damage. Overall, given the extensive connection between Nse5 and components of the SUMO pathway, we speculate that one function of the Smc5/6 complex might be as a scaffold center to enable sumoylation events in budding yeast. PMID:27215325

  12. Synthesis of myo-inositol 1,3,4,5,6-pentakisphosphate from inositol phosphates generated by receptor activation.

    PubMed Central

    Stephens, L R; Hawkins, P T; Barker, C J; Downes, C P

    1988-01-01

    myo-[3H]Inositol 1,3,4,5,6-pentakisphosphate can be made from myo-[3H]inositol 1,4,5-trisphosphate in a rat brain homogenate or soluble fraction. Although D-myo-inositol 3,4,5,6-tetrakisphosphate can be phosphorylated by a soluble rat brain enzyme to give myo-inositol 1,3,4,5,6-pentakisphosphate, it is not an intermediate in the pathway from myo-inositol 1,4,5-trisphosphate. The intermediates in the above pathway are myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 1,3,4-trisphosphate and myo-inositol 1,3,4,6-tetrakisphosphate [Shears, Parry, Tang, Irvine, Michell & Kirk (1987) Biochem. J. 246, 139-147; Balla, Guillemette, Baukal & Catt (1987) J. Biol. Chem. 262, 9952-9955], and it is catalysed by soluble kinase activities of similar anion-exchange mobility and Mr value. Compounds with chromatographic and chemical properties consistent with the structures myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 1,3,4,6-tetrakisphosphate and myo-inositol 3,4,5,6-tetrakisphosphate are present in avian erythrocytes, human 1321 N1 astrocytoma cells and primary-cultured murine bone-marrow-derived macrophages. The amounts of these inositol tetrakisphosphates rise upon muscarinic cholinergic stimulation of the astrocytoma cells or stimulation of macrophages with platelet-activating factor. PMID:2845930

  13. Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

    PubMed

    Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

    2014-07-01

    Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine.

  14. A simple isocratic HPLC method for the simultaneous determination of sinensetin, eupatorin, and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone in Orthosiphon stamineus extracts.

    PubMed

    Yam, Mun Fei; Mohamed, Elsnoussi Ali Hussin; Ang, Lee Fung; Pei, Li; Darwis, Yusrida; Mahmud, Roziahanim; Asmawi, Mohd Zaini; Basir, Rusliza; Ahmad, Mariam

    2012-08-01

    Orthosiphon stamineus extracts contain three flavonoids (3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin) as bioactive substances. Previous reported high performance liquid chromatography- ultraviolet (HPLC-UV) methods for the determination of these flavonoids have several disadvantages, including unsatisfactory separation times and not being well validated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) standard guidelines. A rapid, specific reversed-phase HPLC method with isocratic elution of acetonitrile: isopropyl alcohol: 20mM phosphate buffer (NaH(2)PO(4)) (30:15:55, v/v) (pH 3.5) at a flow-rate of 1ml/minute, a column temperature of 25°C, and ultraviolet (UV) detection at 340 nm was developed. The method was validated and applied for quantification of different types of O stamineus extracts and fractions. The method allowed simultaneous determination of 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin in the concentration range of 0.03052-250 μg/ml. The limits of detection and quantification, respectively, were 0.0076 and 0.061 μg/ml for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, 0.0153 and 0.122 μg/ml for sinensetin and 0.0305 and 0.122 μg/ml for eupatorin. The percent relative standard deviation (% RSD) values for intraday were 0.048-0.368, 0.025-0.135, and 0.05-0.476 for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for intraday precision were 0.333-1.688, 0.722-1.055, and 0.548-1.819, respectively. The accuracy for intraday were 91.25%-103.38%, 94.32%-109.56%, and 92.85%-109.70% for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for interday accuracy were 97.49%-103.92%, 103.58%-104.57%, and 103.9%-105.33%, respectively. The method was found to be simple, accurate and precise and is recommended for routine quality control analysis of O

  15. Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

    PubMed Central

    Brown, Kyle S.; Oestmo, Simen; Pereira, Telmo; Ranhorn, Kathryn L.; Schoville, Benjamin J.; Marean, Curtis W.

    2017-01-01

    There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5–6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, ‘place provisioning’, longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS

  16. Synthesis and study of fluorescence properties of novel pyrazolo[4‧,3‧:5,6]pyrido[2,3-d]pyrimidin-5(6H)-one derivatives

    NASA Astrophysics Data System (ADS)

    Quiroga, Jairo; Acosta, Paola; Ortiz, Alejandro; Insuasty, Braulio; Abonia, Rodrigo

    2015-10-01

    New pyrazolo[4‧,3‧:5,6]pyrido[2,3-d]pyrimidin-5(6H)-one derivatives 5 were prepared by cyclocondensation reaction between heterocyclic o-aminonitriles 3 and carboxylic acids 4 in the presence of sulfuric acid as catalyst. This procedure provides the desired compound in good yield with a simple one-step methodology. The obtained products show interesting fluorescence properties in both solution and solid state; in this way several spectra of absorption and emission were measured for selected compounds 5b, 5e, 5g and 5j, showing a broad and intense emission band around of 470 nm. In other to understand the electronic transition processes, theoretical calculations were performed at TD-DFT level, using B3LYP as functional and 6-31(d,p) as basis set, finding a good agreement with experimental measurements.

  17. 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.

  18. 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

  19. Pharmacokinetics and metabolism of triclopyr 3,5,6-trichloro-2-pyridinyloxyacetic acid) in Fischer 344 rats.

    PubMed

    Timchalk, C; Dryzga, M D; Kastl, P E

    1990-05-14

    Triclopyr, (3,5,6-trichloro-2-pyridinyloxyacetic acid) is the active component of GARLON (trademark of the Dow Chemical Company) brand herbicide. [14C]Triclopyr was administered orally to groups of 5 rats/sex as a single 3 and 60 mg/kg body weight dose and as a multiple 3 mg/kg nonradiolabeled dose for 14 days followed by a single 3 mg [14C]triclopyr/kg dose on day 15. A fourth group (5 rats/sex) was administered a single 3 mg/kg intravenous dose of [14C]triclopyr. In addition, two groups of male rats (3/dose) were used to obtain 14C plasma time-course data and were orally administered [14C]triclopyr at doses of 3 and 60 mg/kg. Between 94 and 97% of the administered radioactivity was recovered, and the principal route of excretion was the urine (89-95%). The feces contained less than 3% of the dose and the expired 14CO2 and cage wash accounted for less than 0.2 and 1% of the dose, respectively. The tissues and carcass accounted for less than 2% of the radioactivity at 72 h post-dosing. [14C]Triclopyr was rapidly and completely absorbed after oral administration of 3 and 60 mg/kg. The radioactivity was cleared from the plasma of male rats at 3 mg/kg in a mono-exponential manner, with an apparent first-order elimination half-life of 3.6 h. The primary difference between the 3 and 60 mg/kg dose kinetics was the saturation of renal elimination of triclopyr through 9 h post-dosing for the 60 mg/kg group. [14C]Triclopyr was primarily excreted unchanged in the urine (81-96% of the urinary radioactivity), although 4 minor urinary metabolites were noted. Aside from the initial saturation of renal elimination of triclopyr at 60 mg/kg, there were no appreciable differences in the absorption, disposition, or metabolism of [14C]triclopyr, based on sex, or prior exposure.

  20. 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.

  1. Inframolecular acid–base and coordination properties towards Na+ and Mg2+ of myo-inositol 1,3,4,5,6-pentakisphosphate: a structural approach to biologically relevant species† †Electronic supplementary information (ESI) available: Application of the Cluster Expansion Method (Table S1); 31P NMR spectra (Fig. S1); Structural details of Ins(1,3,4,5,6)P 5–Mg2+ interaction (Fig. S2); Comparative fit of alternative chemical models for the Ins(1,3,4,5,6)P 5–Na+ system (Fig. S3). See DOI: 10.1039/c2dt31807e Click here for additional data file.

    PubMed Central

    Torres, Julia; Macho, Israel; Gómez, Kerman; Godage, Himali Y.; Riley, Andrew M.; Potter, Barry V. L.; González, Gabriel; Kremer, Carlos

    2013-01-01

    The myo-inositol phosphates (InsPs) are specific signalling metabolites ubiquitous in eukaryotic cells. Although Ins(1,3,4,5,6)P 5 is the second most abundant member of the InsPs family, its certain biological roles are far from being elucidated, in part due to the large number of species formed by Ins(1,3,4,5,6)P 5 in the presence of metal ions. In light of this, we have strived in the past to make a complete and at the same time “biological-user-friendly” description of the Ins(1,3,4,5,6)P 5 chemistry with mono and multivalent cations. In this work we expand these studies focusing on the inframolecular aspects of its protonation equilibria and the microscopic details of its coordination behaviour towards biologically relevant metal ions. We present here a systematic study of the Ins(1,3,4,5,6)P 5 intrinsic acid–base processes, in a non-interacting medium, and over a wide pH range, analyzing the 31P NMR curves by means of a model based on the Cluster Expansion Method. In addition, we have used a computational approach to analyse the energetic and structural features of the protonation and conformational changes of Ins(1,3,4,5,6)P 5, and how they are influenced by the presence of two physiologically relevant cations, Na+ and Mg2+. PMID:23183928

  2. 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.

  3. Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

    PubMed

    Timchalk, C; Finco, D R; Quast, J F

    1997-03-01

    The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey

  4. Synthesis of Natural Homoisoflavonoids Having Either 5,7-Dihydroxy-6-methoxy or 7-Hydroxy-5,6-dimethoxy Groups

    PubMed Central

    Lee, Hyungjun; Yuan, Yue; Rhee, Inmoo; Corson, Timothy W.; Seo, Seung-Yong

    2016-01-01

    Naturally occurring homoisoflavonoids containing either 5,7-dihydroxy-6-methoxy or 7-hydroxy-5,6-dimethoxy groups such as the antiangiogenic homoisoflavanone, cremastranone, were synthesized via three or four linear steps from the known 4-chromenone. This facile synthesis includes chemoselective 1,4-reduction of 4-chromenone and selective deprotection of 3-benzylidene-4-chromanone a containing C7-benzyloxy group. PMID:27529212

  5. Extrusion of microtubule doublet outer dense fibers 5-6 associating with fibrous sheath sliding in mouse sperm flagella.

    PubMed

    Si, Y; Okuno, M

    1995-11-01

    Our previous experiments (Si and Okuno [1993a] Exp. Cell Res., 208:170-174) provided evidence that the fibrous sheath (FS) slid headward to middle piece in the activated mouse sperm flagellum when doublet microtubules together with their outer dense fibers (ODFs) extruded from the axoneme. Of the extruded doublet-ODFs, however, which one was responsible for the FS sliding remained unresolved. The present study demonstrated that the FS sliding and the order of doublet-ODFs extrusion in mouse sperm flagella were trypsin concentration dependent. Under the condition of mild trypsinization (0.1 micrograms/ml), only doublet-ODFs 4, 5-6 (doublet-ODFs 5 and 6 were always paired), and 7 extruded from the axoneme. Furthermore, the extrusion of doublet-ODFs 5-6 was identified to precede doublet-ODFs 4 and 7, and was considered the candidate responsible for FS sliding. In contrast, the high-concentration trypsinization (4 micrograms/ml) led to extrusion of doublet-ODFs 1, 2, and 9 following doublet-ODFs 4, 5-6, and 7. FS sliding, however, did not occur.

  6. Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan

    PubMed Central

    Chang, Tao-Hsin; Hsieh, Fu-Lien; Zebisch, Matthias; Harlos, Karl; Elegheert, Jonathan; Jones, E Yvonne

    2015-01-01

    Wnt signalling regulates multiple processes including angiogenesis, inflammation, and tumorigenesis. Norrin (Norrie Disease Protein) is a cystine-knot like growth factor. Although unrelated to Wnt, Norrin activates the Wnt/β-catenin pathway. Signal complex formation involves Frizzled4 (Fz4), low-density lipoprotein receptor related protein 5/6 (Lrp5/6), Tetraspanin-12 and glycosaminoglycans (GAGs). Here, we report crystallographic and small-angle X-ray scattering analyses of Norrin in complex with Fz4 cysteine-rich domain (Fz4CRD), of this complex bound with GAG analogues, and of unliganded Norrin and Fz4CRD. Our structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4CRD. These results explain numerous disease-associated mutations. Comparison with the Xenopus Wnt8–mouse Fz8CRD complex reveals Norrin mimics Wnt for Frizzled recognition. The production and characterization of wild-type and mutant Norrins reported here open new avenues for the development of therapeutics to combat abnormal Norrin/Wnt signalling. DOI: http://dx.doi.org/10.7554/eLife.06554.001 PMID:26158506

  7. Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

    PubMed Central

    Reichstetter, Sandra; Castillo, Gerardo M.; Rubinstein, Israel; Nishimoto-Ashfield, Akiko; Lai, ManShun; Jones, Cynthia C.; Banjeree, Aryamitra; Lyubimov, Alex; Bloedow, Duane C.; Bogdanov, Alexei; Bolotin, Elijah M.

    2013-01-01

    Purpose To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP). Methods VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined. Results Both formulations significantly extend in vivo residence time compared to unformulated VIP. Formulation toxicity is dependent on loading percentage, showing major differences between the two carrier types. Both formulations increase in vivo potency of unformulated VIP and show acute MTDs at least 140 times lower than unformulated VIP, but still at least 100 times higher than the anticipated highest human dose, 1–5 μg/kg. These nanocarriers prevented a significant drop in arterial blood pressure compared to unformulated VIP. Conclusions While both carriers enhance in vivo residence time compared to unformulated VIP and reduce the drop in blood pressure immediately after injection, PGC is the excipient of choice to extend residence time and improve the safety of potent therapeutic peptides such as VIP. PMID:23224976

  8. Higher-Order Modes of Modulation Instability in Bose-Einstein Condensates with a Time-Dependent Three-Dimensional Parabolic Potential

    NASA Astrophysics Data System (ADS)

    Zong, Feng-De; Yan, Yu-Sheng; Shen, Sen-Ting

    2014-10-01

    By the similarity reduction and Darboux transformation, we derive higher-order modes of three-dimensional Bose-Einstein condensate modulation instability in the nonautonomous Gross-Pitaevskii equation and manipulate them by regulating the time-dependent potential and gain. Firstly, by the similarity reduction, the (3+1)-dimensional nonautonomous Gross-Pitaevskii equation reduces to a (1+1)-dimensional standard nonlinear Schrödinger equation with constant coefficients. Then, considering the Akhmediev breather solution as the first-order modulation instability solution of the higher-order modes of Bose-Einstein condensate modulation instability, we achieve the Nth-order (N = 2, 3, 4, and 5) modulation instability solutions by the Darboux transformation. Finally, we verify the stable higher-order modes of Bose-Einstein condensate modulation instability and manipulate them by direct numerical simulation. The obtained results may raise the possibility of related experiments and potential applications in Bose-Einstein condensates and other related fields.

  9. Shortened time interval between colorectal cancer diagnosis and risk testing for hereditary colorectal cancer is not related to higher psychological distress.

    PubMed

    Landsbergen, K M; Prins, J B; Brunner, H G; Hoogerbrugge, N

    2011-03-01

    Current diagnostic practices have shortened the interval between colorectal cancer (CRC) diagnosis and genetic analysis for Lynch syndrome by MSI-testing. We studied the relation of time between MSI-testing since CRC diagnosis (MSI-CRC interval) and psychological distress. We performed a cross-sectional study in 89 patients who had previously been treated for CRC. Data were collected during MSI-testing after genetic counseling. Psychological distress was measured with the IES, the SCL-90 and the POMS; social issues with the ISS, ISB and the ODHCF. The median time of MSI-CRC interval was 24 months (range 0-332), with 23% of the patients diagnosed less than 12 months and 42% more than 36 months prior to MSI-testing. In 34% of the patients cancer specific distress was high (IES scores >26). Mean psychopathology (SCL-90) scores were low, mean mood states (POMS) scores were moderate. Interval MSI-CRC was not related to psychological distress. High cancer specific distress was reported by 24% of patients diagnosed with CRC less than 12 months ago versus 39 and 35% by those diagnosed between 12 and 36 months and more than 36 months ago respectively. Distress was positively related to female gender (P = 0.04), religiousness (P = 0.01), low social support (P = 0.02) and difficulties with family communication (P < 0.001). Shortened time interval between CRC diagnosis and MSI-testing is not associated with higher psychological distress. Females, religious persons, those having low social support and those reporting difficulties communicating hereditary colorectal cancer with relatives are at higher risk for psychological distress.

  10. Preparation and physicochemical characterization of a solid dispersion of (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T) and polyvinylpyrrolidone.

    PubMed

    Cao, Sa-Li; Hou, Peng; Li, Bin; Fu, Jing; Yin, Xing-Bin; Dang, Xiao-Fang; Yang, Chun-Jing; Zhang, Jin; Zhang, Hui; Lei, Hai-Min; Ni, Jian

    2015-11-01

    Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.

  11. Chemical, pulse radiolysis and density functional studies of a new, labile 5,6-indolequinone and its semiquinone.

    PubMed

    Pezzella, Alessandro; Crescenzi, Orlando; Natangelo, Anna; Panzella, Lucia; Napolitano, Alessandra; Navaratnam, Suppiah; Edge, Ruth; Land, Edward J; Barone, Vincenzo; d'Ischia, Marco

    2007-03-02

    The chemical and spectroscopic characterization of 5,6-indolequinones and their semiquinones, key transient intermediates in the oxidative conversion of 5,6-dihydroxyindoles to eumelanin biopolymers, is a most challenging task. In the present paper, we report the characterization of a novel, relatively long-lived 5,6-indolequinone along with its semiquinone using an integrated chemical, pulse radiolytic, and computational approach. The quinone was obtained by oxidation of 5,6-dihydroxy-3-iodoindole (1a) with o-chloranil in cold ethyl acetate or aqueous buffer: it displayed electronic absorption bands around 400 and 600 nm, was reduced to 1a with Na2S2O4, and reacted with o-phenylenediamine to give small amounts of 3-iodo-1H-pyrrolo[2,3-b]phenazine (2). The semiquinone exhibited absorption maxima at 380 nm (sh) and 520 nm and was detected as the initial species produced by pulse radiolytic oxidation of 1a at pH 7.0. DFT investigations indicated the 6-phenoxyl radical and the N-protonated radical anion as the most stable tautomers for the neutral and anion forms of the semiquinone, respectively. Calculated absorption spectra in water gave bands at 350 (sh) and 500 nm for the neutral form and at 310 and 360 (sh) nm for the anion. Disproportionation of the semiquinone with fast second-order kinetics (2k = 1.1 x 1010 M-1 s-1) gave a chromophore with absorption bands resembling those of chemically generated 1a quinone. Computational analysis predicted 1a quinone to exist in vacuo as the quinone-methide tautomer, displaying low energy transitions at 380 and 710 nm, and in water as the o-quinone, with calculated absorption bands around 400 and 820 nm. A strong participation of a p orbital on the iodine atom in the 360-380 nm electronic transitions of the o-quinone and quinone-methide was highlighted. The satisfactory agreement between computational and experimental electronic absorption data would suggest partitioning of 1a quinone between the o-quinone and quinone

  12. Novel selectfluor and deoxo-fluor-mediated rearrangements. New 5(6)-methyl and phenyl methanopyrrolidine alcohols and fluorides.

    PubMed

    Krow, Grant R; Lin, Guoliang; Moore, Keith P; Thomas, Andrew M; DeBrosse, Charles; Ross, Charles W; Ramjit, Harri G

    2004-05-13

    Stereoselective syntheses of novel 5,6-difunctionalized-2-azabicyclo[2.1.1]hexanes containing 5-anti-fluoro or hydroxyl in one methano bridge and a variety of syn- or anti-chloro, fluoro, hydroxy, methyl, or phenyl substituents in the other methano bridge have been effected. Rearrangements of iodides to alcohols were initiated using Selectfluor. Rearrangement of alcohols to fluorides was initiated using Deoxo-Fluor. Ring opening of 2-azabicyclo[2.2.0]hex-5-ene exo-epoxide with organocopper reagents is regioselective at C(5).

  13. Emission spectra and kinetics of copolymer films of styrene and 2,3,4,5,6-pentafluorostyrene

    NASA Technical Reports Server (NTRS)

    O'Connor, Donald B.; Scott, Gary W.; Coulter, Daniel R.; Yavrouian, Andre

    1991-01-01

    The temperature-dependent steady-state emission spectra and fluorescence kinetics of copolymer films of styrene and 2,3,4,5,6-pentafluorostyrene are reported. The polystyrene excimer emission is efficiently quenched in the presence of relatively small amounts of the pentafluorophenyl quencher in spite of the fact that direct energy transfer from the excimer to the quencher chromophores is not possible. The quenching of the polystyrene excimer emission at room temperature and of the polystyrene monomer emission at 13 K is attributed to the interception of the migrating monomer excitation by the quencher. The data suggest that this quenching mechanism is independent of temperature.

  14. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  15. Inframolecular acid-base and coordination properties towards Na(+) and Mg(2+) of myo-inositol 1,3,4,5,6-pentakisphosphate: a structural approach to biologically relevant species.

    PubMed

    Veiga, Nicolás; Torres, Julia; Macho, Israel; Gómez, Kerman; Godage, Himali Y; Riley, Andrew M; Potter, Barry V L; González, Gabriel; Kremer, Carlos

    2013-05-07

    The myo-inositol phosphates (InsPs) are specific signalling metabolites ubiquitous in eukaryotic cells. Although Ins(1,3,4,5,6)P(5) is the second most abundant member of the InsPs family, its certain biological roles are far from being elucidated, in part due to the large number of species formed by Ins(1,3,4,5,6)P(5) in the presence of metal ions. In light of this, we have strived in the past to make a complete and at the same time "biological-user-friendly" description of the Ins(1,3,4,5,6)P(5) chemistry with mono and multivalent cations. In this work we expand these studies focusing on the inframolecular aspects of its protonation equilibria and the microscopic details of its coordination behaviour towards biologically relevant metal ions. We present here a systematic study of the Ins(1,3,4,5,6)P(5) intrinsic acid-base processes, in a non-interacting medium, and over a wide pH range, analyzing the (31)P NMR curves by means of a model based on the Cluster Expansion Method. In addition, we have used a computational approach to analyse the energetic and structural features of the protonation and conformational changes of Ins(1,3,4,5,6)P(5), and how they are influenced by the presence of two physiologically relevant cations, Na(+) and Mg(2+).

  16. Higher-order split operator schemes for solving the Schrödinger equation in the time-dependent wave packet method: applications to triatomic reactive scattering calculations.

    PubMed

    Sun, Zhigang; Yang, Weitao; Zhang, Dong H

    2012-02-14

    The efficiency of the numerical propagators for solving the time-dependent Schrödinger equation in the wave packet approach to reactive scattering is of vital importance. In this Perspective, we first briefly review the propagators used in quantum reactive scattering calculations and their applications to triatomic reactions. Then we present a detailed comparison of about thirty higher-order split operator propagators for solving the Schrödinger equation with their applications to the wave packet evolution within a one-dimensional Morse potential, and the total reaction probability calculations for the H + HD, H + NH, H + O(2), and F + HD reactions. These four triatomic reactions have quite different dynamic characteristics and thus provide a comprehensive picture of the relative advantages of these higher-order propagation methods for describing reactive scattering dynamics. Our calculations reveal that the most often used second-order split operator method is typically more efficient for a direct reaction, particularly for those involving flat potential energy surfaces. However, the optimal higher-order split operator methods are more suitable for a reaction with resonances and intermediate complexes or a reaction experiencing potential energy surface with fluctuations of considerable amplitude. Three 4th-order and one 6th-order split operator methods, which are most efficient for solving reactive scattering in various conditions among the tested ones, are recommended for general applications. In addition, a brief discussion on the relative performance between the Chebyshev real wave packet method and the split operator method is given. The results in this Perspective are expected to stimulate more applications of (high-order) split operators to the quantum reactive scattering calculation and other related problems.

  17. Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.

    PubMed

    Červenka, Luděk; Škaroupková, Petra; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz

    2016-10-01

    The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto-caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF.

  18. [Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls].

    PubMed

    Sánchez-Martín, José R; Azurmendi Imaz, Aitziber; Fano Ardanaz, Eduardo; Braza Lloret, Francisco; Muñoz Sánchez, José M; Carreras de Alba, María R

    2009-02-01

    Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls. This study explores the relationship between androgen levels, parenting styles, and physical, verbal, and indirect aggression measures in 5-6-year-old children. 129 children (60 boys and 69 girls) were assessed in relation to their aggression levels using a peer-rating technique. Parents completed the Parenting Styles and Dimensions Questionnaire, from which the different parenting styles were obtained. Testosterone, androstenedione and dehydroepiandrosterone (DHEA) were measured using an enzymoimmunoassay technique in saliva samples. A regression analysis indicated that the directive mother-androstenedione interaction at the age of 5 was predictive of physical aggression at the age of 6. In specific terms, the results showed that, in boys with high androstenedione levels, directive maternal behavior is associated with physical aggression. The results are subsequently discussed in light of postulates related to parenting characteristic of developmental psychology and we suggest a potential link of our results with the hypothesis of maternal dominance.

  19. Polarization components in π0 photoproduction at photon energies up to 5.6 GeV

    SciTech Connect

    Luo, W.; Brash, E. J.; Gilman, R.; Jones, M. K.; Meziane, M.; Pentchev, L.; Perdrisat, C. F; Puckett, A. J.R.; Punjabi, V.; Wesselmann, F. R.; Marsh, A.; Matulenko, Y.; Maxwell, J.; Meekins, D.; Melnik, Y.; Miller, J.; Mkrtchyan, A.; Mkrtchyan, H.; Moffit, B.; Moreno, O.; Mulholland, J.; Narayan, A.; Nuruzzaman, .; Nedev, S.; Piasetzky, E.; Pierce, W.; Piskunov, N. M.; Prok, Y.; Ransome, R. D.; Razin, D. S.; Reimer, P. E.; Reinhold, J.; Rondon, O.; Shabestari, M.; Shahinyan, A.; Shestermanov, K.; Sirca, S.; Sitnik, I.; Smykov, L.; Smith, G.; Solovyev, L.; Solvignon, P.; Strakovsky, I. I; Subedi, R.; Suleiman, R.; Tomasi-Gustafsson, E.; Vasiliev, A.; Veilleux, M.; Wood, S.; Ye, Z.; Zanevsky, Y.; Zhang, X.; Zhang, Y.; Zheng, X.; Zhu, L.; Ahmidouch, A.; Albayrak, I.; Aniol, K. A.; Arrington, J.; Asaturyan, A.; Ates, O.; Baghdasaryan, H.; Benmokhtar, F.; Bertozzi, W.; Bimbot, L.; Bosted, P.; Boeglin, W.; Butuceanu, C.; Carter, P.; Chernenko, S.; Christy, M. E.; Commisso, M.; Cornejo, J. C.; Covrig, S.; Danagoulian, S.; Daniel, A.; Davidenko, A.; Day, D.; Dhamija, S.; Dutta, D.; Ent, R.; Frullani, S.; Fenker, H.; Frlez, E.; Garibaldi, F.; Gaskell, D.; Gilad, S.; Goncharenko, Y.; Hafidi, K.; Hamilton, D.; Higinbotham, D. W.; Hinton, W.; Horn, T.; Hu, B.; Huang, J.; Huber, G. M.; Jensen, E.; Kang, H.; Keppel, C.; Khandaker, M.; King, P.; Kirillov, D.; Kohl, M.; Kravtsov, V.; Kumbartzki, G.; Li, Y.; Mamyan, V.; Margaziotis, D. J.; Markowitz, P.

    2012-05-31

    We present new data for the polarization observables of the final state proton in the 1H(→ γ, → p)π0 reaction. These data can be used to test predictions based on hadron helicity conservation (HHC) and perturbative QCD (pQCD). These data have both small statistical and systematic uncertainties, and were obtained with beam energies between 1.8 and 5.6 GeV and for π0 scattering angles larger than 75{sup o} in center-of-mass (c.m.) frame. The data extend the polarization measurements data base for neutral pion photoproduction up to Eγ = 5.6 GeV. The results show non-zero induced polarization above the resonance region. The polarization transfer components vary rapidly with the photon energy and π0 scattering angle in the center-of-mass frame. This indicates that HHC does not hold and that the pQCD limit is still not reached in the energy regime of this experiment.

  20. Polarization components in π0 photoproduction at photon energies up to 5.6 GeV

    DOE PAGES

    Luo, W.; Brash, E. J.; Gilman, R.; ...

    2012-05-31

    We present new data for the polarization observables of the final state proton in the 1H(→ γ, → p)π0 reaction. These data can be used to test predictions based on hadron helicity conservation (HHC) and perturbative QCD (pQCD). These data have both small statistical and systematic uncertainties, and were obtained with beam energies between 1.8 and 5.6 GeV and for π0 scattering angles larger than 75{sup o} in center-of-mass (c.m.) frame. The data extend the polarization measurements data base for neutral pion photoproduction up to Eγ = 5.6 GeV. The results show non-zero induced polarization above the resonance region. Themore » polarization transfer components vary rapidly with the photon energy and π0 scattering angle in the center-of-mass frame. This indicates that HHC does not hold and that the pQCD limit is still not reached in the energy regime of this experiment.« less

  1. Muscular response to physiologic tensile stretch of the caprine c5/6 facet joint capsule: dynamic recruitment thresholds and latencies.

    PubMed

    Azar, Nadia R; Kallakuri, Srinivasu; Chen, Chaoyang; Cavanaugh, John M

    2011-11-01

    This study examined the cervical muscle response to physiologic, high-rate (100 mm/s) tensile facet joint capsule (FJC) stretch. Six in-vivo caprine C5/6 FJC preparations were subjected to an incremental tensile loading paradigm. EMG activity was recorded from the right trapezius (TR) and multifidus (MF) muscle groups at the C5 and C6 levels; and from the sternomastoid (SM) and longus colli (LC) muscle groups bilaterally at the C5/6 level; during FJC stretch. Capsule load during the displacement applications was recorded via a miniature load cell, and 3D capsule strains (based on stereoimaging of an array of markers on the capsule surface) were reconstructed using finite element methods. EMG traces from each muscle were examined for onset of muscular activity. Capsule strains and loads at the time of EMG onset were recorded for each muscle, as was the time from the onset of FJC stretch to the onset of muscle activity. All muscles were responsive to physiologic high-rate FJC stretch. The deep muscles (MF and LC) were recruited at significantly smaller capsule loads and onset latencies than the superficial muscles (TR and SM). MF activation strain was significantly smaller than LC and TR activation strains. These data were also compared to previously published low-rate data. MF was the first muscle group to be recruited regardless of the activation criterion under consideration (i.e. strain, load, or latency) or the rate of FJC stretch. LC recruitment occurred significantly sooner under high-rate vs. low-rate FJC stretch. The results of this study provide further evidence of extensive ligamento-muscular reflex pathways between the FJC and the cervical musculature, which are responsive to both low-rate and high-rate FJC stretch. These data add to our knowledge of the dynamic response of paraspinal muscles relative to facet joint motion and provide a unique contribution to enhance the precision of computer-simulated impacts.

  2. 5,6-EET Is Released upon Neuronal Activity and Induces Mechanical Pain Hypersensitivity via TRPA1 on Central Afferent Terminals

    PubMed Central

    Sisignano, Marco; Park, Chul-Kyu; Angioni, Carlo; Zhang, Dong Dong; von Hehn, Christian; Cobos, Enrique J.; Ghasemlou, Nader; Xu, Zhen-Zhong; Kumaran, Vigneswara; Lu, Ruirui; Grant, Andrew; Fischer, Michael J. M.; Schmidtko, Achim; Reeh, Peter; Ji, Ru-Rong; Woolf, Clifford J.; Geisslinger, Gerd; Scholich, Klaus; Brenneis, Christian

    2012-01-01

    Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient receptor potential (TRP) channel activation in nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, 5,6-EET levels increased in dorsal root ganglia (DRGs) and the dorsal spinal cord, and 5,6-EET is released from activated sensory neurons in vitro. 5,6-EET potently induced a calcium flux (100 nm) in cultured DRG neurons that was completely abolished when TRPA1 was deleted or inhibited. In spinal cord slices, 5,6-EET dose dependently enhanced the frequency, but not the amplitude, of spontaneous EPSCs (sEPSCs) in lamina II neurons that also responded to mustard oil (allyl isothiocyanate), indicating a presynaptic action. Furthermore, 5,6-EET-induced enhancement of sEPSC frequency was abolished in TRPA1-null mice, suggesting that 5,6-EET presynaptically facilitated spinal cord synaptic transmission by TRPA1. Finally, in vivo intrathecal injection of 5,6-EET caused mechanical allodynia in wild-type but not TRPA1-null mice. We conclude that 5,6-EET is synthesized on the acute activation of nociceptors and can produce mechanical hypersensitivity via TRPA1 at central afferent terminals in the spinal cord. PMID:22553041

  3. Bioconcentration of 5,5',6-trichlorobiphenyl and pentachlorophenol in the midge, Chironomus riparius, as measured by a pharmacokinetic model

    USGS Publications Warehouse

    Lydy, M.J.; Hayton, W.L.; Staubus, A.E.; Fisher, S.W.

    1994-01-01

    A two compartment pharmacokinetic model was developed which describes the uptake and elimination of 5,5',6-trichlorobiphenyl (TCB) and pentachlorophenol (PCP) in the midge, Chironomus riparius. C. riparius were exposed to nominal TCB (2 ??g L-1) and PCP (9 ??g L-1) concentrations during a 16 h static uptake phase. Depuration was determined over approximately 45 h using a flowthrough system without feeding. The uptake clearance (P) was 330 ?? 61 ml g-1 midge h-1 for TCB and 55 ?? 4 ml g-1 midge h-1 for PCP, while measured bioconcentration factors (BCF) were 35,900 and 458 for TCB and PCP, respectively. Overall, the clearance-volume- based pharmacokinetic model predicted BCF values that were consistent with published values as well as with BCF values obtained from the octanol-water partition coefficient (K(ow)).

  4. Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.

    PubMed

    Park, Bora; Awasthi, Divya; Chowdhury, Soumya R; Melief, Eduard H; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

    2014-05-01

    Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM.

  5. Kinetics of inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole on calf thymus casein kinase II.

    PubMed

    Zandomeni, R O

    1989-09-01

    The adenosine analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) is a specific inhibitor for RNA polymerase II transcription in vivo and in vitro [Tamm + Sehgal (1978) Adv. Virus Res. 22, 187-258; Zandomeni & Weinmann (1984) J. Biol. Chem. 259, 14804-14811]. The effect on RNA polymerase II-specific transcription seems to be mediated by its inhibition of nuclear casein kinase II [Zandomeni, Carrera-Zandomeni, Shugar & Weinmann (1986) J. Biol. Chem. 261, 3414-3419]. Inhibition studies indicated that DRB acted as a mixed-type inhibitor with respect to casein and as a competitive inhibitor with respect to the nucleotide phosphate donor substrates. The DRB inhibition constant is 7 microM for the calf thymus casein kinase II, with regard to both ATP and GTP.

  6. SAMS Acceleration Measurements on Mir from May 1997 to June 1998 (NASA Increments 5, 6, and 7)

    NASA Technical Reports Server (NTRS)

    DeLombard, Richard

    1999-01-01

    During NASA Increments 5, 6, and 7 (May 1997 to June 1998), about eight gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station Mir. The data were recorded on twenty-seven optical disks which were returned to Earth on Orbiter missions STS-86, STS-89, and STS-91. During these increments, SAMS data were collected in the Priroda module to support various microgravity experiments. This report points out some of the salient features of the microgravity acceleration environment to which the experiments were exposed. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous Mir increment summary reports prepared by the Principal Investigator Microgravity Services project.

  7. Time Is Money...and the Enemy of College Completion: Transform American Higher Education to Boost Completion and Reduce Costs. Testimony before the United States House of Representatives Subcommittee on Higher Education and Workforce Training

    ERIC Educational Resources Information Center

    Jones, Stan

    2012-01-01

    This paper presents Stan Jones' testimony before the United States House of Representatives Subcommittee on Higher Education and Workforce Training. In his testimony, he talks about a new American majority of students that is emerging on campuses, especially at community colleges. These students must delicately balance long hours at jobs they must…

  8. Isolation of oligomers of 5,6-dihydroxyindole-2-carboxylic acid from the eye of the catfish

    PubMed Central

    Ito, Shosuke; Nicol, J. A. Colin

    1974-01-01

    The reflecting material of the tapetum lucidum of the sea catfish (Arius felis) was chromatographed on Sephadex LH-20 in methanol–dimethyl sulphoxide–formic acid. Two components were present: one, showing an absorption maximum at 330nm, was tapetal pigment; the other, at 257nm, was an associated nucleoside. The tapetal pigment was extracted in methanol–HCl and isolated by adsorption chromatography on Sephadex LH-20. It yielded a methoxy methyl ester on treatment with diazomethane, and permanganate oxidation gave pyrrole-2,3,5-tricarboxylic acid. From the information provided by u.v. and i.r. spectra of the pigment and its methoxy methyl ester, from elemental analyses and from the oxidation products, we suggest that the tapetal pigment is derived from oxidative coupling of 5,6-dihydroxyindole-2-carboxylic acid. A molecular-weight determination and chromatography of the methoxy methyl ester indicate that the pigment is a mixture of oligomers, among which the tetramers probably predominate. We consider that the monomers are joined mainly by C-C linkages at positions 4 and 7. A synthetic pigment having spectral properties nearly identical with those of the natural pigment was prepared by enzymic oxidation of 5,6-dihydroxyindole-2-carboxylic acid with mushroom tyrosinase. The identity of the tapetal pigment with the synthetic pigment was further confirmed by comparing u.v. and i.r. spectra of their methoxy methyl esters. Formation of the tapetal pigment from tyrosine and relationships of the tapetal pigment to melanin are discussed. PMID:4464851

  9. Mn(II) complexes containing the polypyridylic chiral ligand (-)-pinene[5,6]bipyridine. Catalysts for oxidation reactions.

    PubMed

    Rich, Jordi; Rodríguez, Montserrat; Romero, Isabel; Vaquer, Lydia; Sala, Xavier; Llobet, Antoni; Corbella, Montserrat; Collomb, Marie-Noëlle; Fontrodona, Xavier

    2009-10-14

    A series of mononuclear and dinuclear chiral manganese(II) complexes containing the neutral bidentate chiral nitrogen ligand (-)-pinene[5,6]bipyridine, (-)-L, were prepared from different manganese salts. The chirality in these complexes arises from the pinene ring that has been fused to the 5,6 positions of one pyridine group of the bipyridine ligand. These complexes have been characterized through analytical, spectroscopic (IR, UV/Vis, ESI-MS) and electrochemical techniques (cyclic voltammetry). Single X-ray structure analysis revealed a five-coordinated Mn(II) ion in [{MnCl((-)-L)}2(mu-Cl)2] (2), [{Mn((-)-L)}2(mu-OAc)3](PF6) (3) and [MnCl2(H2O)((-)-L)] (4) and a six-coordinated one in [MnCl2((-)-L)2] (5), [Mn(CF3SO3)2((-)-L)2] (6) and [Mn(NO3)(H2O)((-)-L)2)](NO3) (7). The magnetic properties of the binuclear compounds 2 and 3 have been studied. Both compounds show a weak antiferromagnetic coupling (2, J = -0.22 cm(-1); 3, J = -0.85 cm(-1)). The catalytic activity of the whole set of complexes has been tested with regard to the epoxidation of aromatic alkenes with peracetic acid. In the particular case of styrene, good selectivities and moderate enantioselectivities were obtained. Furthermore, total retention of the initial cis configuration was achieved when epoxidizing cis-beta-methylstyrene with the chloride complexes. In general, the epoxidation activity of these manganese complexes is strongly dependent on the steric encumbrance of the substrates employed.

  10. An X-ray characterization of the central region of the supernova remnant G332.5-5.6

    NASA Astrophysics Data System (ADS)

    Suárez, A. E.; Combi, J. A.; Albacete-Colombo, J. F.; Paron, S.; García, F.; Miceli, M.

    2015-11-01

    Aims: We present an X-ray analysis of the central region of supernova remnant (SNR) G332.5-5.6 through an exhaustive analysis of XMM-Netwon observations with complementary infrared observations. We characterize and discuss the origin of the observed X-ray morphology, which presents a peculiar plane edge over the west side of the central region. Methods: The morphology and spectral properties of the X-ray SNR were studied using a single full frame XMM-Newton observation in the 0.3 to 10.0 keV energy band. Archival infrared WISE observations at 8, 12 and 24 μm were also used to investigate the properties of the source and its surroundings at different wavelengths. Results: The results show that the extended X-ray emission is predominantly soft (0.3-1.2 keV) and peaks around 0.5 keV, which shows that it is an extremely soft SNR. X-ray emission correlates very well with central regions of bright radio emission. On the west side the radio/X-ray emission displays a plane-like feature with a terminal wall where strong infrared emission is detected. Our spatially resolved X-ray spectral analysis confirms that the emission is dominated by weak atomic emission lines of N, O, Ne, and Fe, all of them undetected in previous X-ray studies. These characteristics suggest that the X-ray emission is originated in an optically thin thermal plasma, whose radiation is well fitted by a non-equilibrium ionization collisional plasma (VNEI) X-ray emission model. Our study favors a scenario where G332.5-5.6 is expanding in a medium with an abrupt density change (the wall), likely a dense infrared emitting region of dust on the western side of the source.

  11. Localization of a Gene for Keratoconus to a 5.6-Mb Interval on 13q32

    PubMed Central

    Gajecka, Marzena; Radhakrishna, Uppala; Winters, Daniel; Nath, Swapan K.; Rydzanicz, Malgorzata; Ratnamala, Uppala; Ewing, Kimberly; Molinari, Andrea; Pitarque, Jose A.; Lee, Kwanghyuk; Leal, Suzanne M.; Bejjani, Bassem A.

    2009-01-01

    Purpose Keratoconus (KTCN) is a noninflammatory thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and reduced visual acuity. Several loci responsible for a familial form of KTCN have been mapped, however; no mutations in any genes have been identified for any of these loci. There is also evidence that VSX1 and SOD1 may be involved in the etiology of KTCN. The purpose of this study was to verify the available data and to identify a new keratoconus susceptibility locus. Methods KTCN without other ocular or systemic features was diagnosed in 18 families. VSX1 and SOD1 sequencing was performed on affected individuals and control subjects. Genomewide linkage analysis was then performed in all families using polymorphic microsatellite markers with an average spacing of 5 cM. Next, single-nucleotide polymorphism (SNP) arrays, fluorescence in situ hybridization (FISH) analysis, and a comparative genomic hybridization array were used in one family to assess a candidate region on 13q32. Results All previously reported KTCN loci were excluded. VSX1 and SOD1 were sequenced, and no potentially functional variants were found. One KTCN family yielded a maximum multipoint parametric LOD score of 4.1 and multipoint non-parametric linkage (NPL) LOD score of 3.2. Multipoint linkage and haplotype analysis narrowed the locus to a 5.6-Mb region between the SNPs rs9516572 and rs3825523 on 13q32. Conclusions The results exclude VSX1 and SOD1 as potential disease-causing genes in these families and localize a novel gene for keratoconus to a 5.6-Mb interval on 13q32. PMID:19011015

  12. Molecular docking studies of (X-methylphenyl)-5-nitro-6-amino-3-pyridinecarboxmide (X=2,3,4,5,6) as potential inhibitors for Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Premkumar, S.; Asath, R. Mohamed; Rekha, T. N.; Jawahar, A.; Mathavan, T.; Benial, A. Milton Franklin

    2016-05-01

    An insilico and density functional theory (DFT) calculations were carried out for (X-methylphenyl)-5-nitro-6-amino-3-pyridinecarboxmide (X-MPNAPC),{X=2,3,4,5,6} to evaluate the potential inhibitors for Alzheimer's disease. The molecular structure of 2-MPNAPC, 3-MPNAPC, 4-MPNAPC, 5-MPNAPC and 6-MPNAPC molecules was optimized by the DFT/B3LYP method with cc-pVTZ basis set using the Gaussian 09 program. The inhibitory nature of the molecules against enzyme acetylcholinesterase (AChE) catalyzes was evaluated by molecular docking studies. The molecular docking parameters such as binding energy, inhibition constant and intermolecular energy were calculated by the AutoDock 4.0 software. The higher binding energy, intermolecular energy and lower inhibition constant values suggested that the 2-MPNAPC molecule has higher inhibitory nature against the AChE catalyzes, which confirm that the 2-MPNAPC molecule is a potential inhibitor for the Alzheimer's disease. The molecular reactivity was also studied by the frontier molecular orbitals analysis.

  13. Collective Bargaining in Higher Education: Leadership in Uncertain Times. Proceedings of the Annual Conference of the National Center for the Study of Collective Bargaining in Higher Education and the Professions (19th, New York, New York, March 1991).

    ERIC Educational Resources Information Center

    Gibbons, Joan A., Ed.; Johnson, Beth H., Ed.

    This proceedings document discusses academic leadership in uncertain times, the need for a cooperative model of collective bargaining to provide administration and faculty the flexibility required to respond to changing times, who should bargain for whom and for what, readiness of the next generation to lead, and retirement issues for college…

  14. Divided We Fail: Why It's Time for a Broader, More Inclusive Conversation on the Future of Higher Education. A Final Report on the 2013 National Issues Forums

    ERIC Educational Resources Information Center

    Johnson, Jean

    2014-01-01

    At state and institutional levels, leaders are discussing and enacting policy changes that could shape the future of higher education for decades-especially public higher education. But when citizens talk about the mission of higher education today, their conversations are different from those of policymakers. How do their values and concerns…

  15. Absolute rate constants for the quenching of reactive excited states by melanin and related 5,6-dihydroxyindole metabolites: implications for their antioxidant activity.

    PubMed

    Zhang, X; Erb, C; Flammer, J; Nau, W M

    2000-05-01

    The triplet-excited state of benzophenone and the singlet-excited state of 2,3-diazabicyclo[2.2.2]oct-2-ene (Fluorazophore-P) have been employed as kinetic probes to obtain information on the antioxidant activity of the skin and eye pigment melanin and its biogenetic precursors 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). The excited states were generated by the laser-flash photolysis technique and their reaction kinetics was examined by time-resolved transient absorption or fluorescence spectroscopy, respectively. The reaction between triplet benzophenone and DHI produced with unit efficiency the corresponding 6O-centered semiquinone radical, which was characterized by its characteristic transient absorption. The quenching rate constants for DHI (3.1-8.4 x 10(9) M-1 s-1) and DHICA (3.3-5.5 x 10(9) M-1 s-1) were near the diffusion-controlled limit, indicating excellent antioxidant properties. Kinetic solvent effects were observed. The reactivity of synthetic melanin, assessed through the quenching rate constant of Fluorazophore-P and normalized to the number of monomer units, was more than one order of magnitude lower (2.7 x 10(8) M-1 s-1) than that of its precursors. The trend of the quenching rate constants, i.e. DHI > DHICA approximately alpha-tocopherol > melanin, along with the preferential solubility of DHICA in aqueous environments, serves to account for several experimental results from biochemical studies on the inhibition of lipid peroxidation by these natural antioxidants.

  16. Water detection by "turn on" fluorescence of the quinone-containing complexes [Ru(phen)2(1,10-phenanthroline-5,6-dione)2+] and [Ru(phenanthroline-5,6-dione)3]2+.

    PubMed

    Poteet, Steven A; MacDonnell, Frederick M

    2013-10-07

    Addition of water to the quinone functions in [Ru(phen)2(pdn)](2+) (1) and [Ru(pdn)3](2+) (2) (where phen = 1,10-phenanthroline and pdn = 1,10-phenanthroline-5,6-dione) turns on fluorescence at 605 nm, as formation of the geminal diol eliminates the predominant quinone-based non-radiative decay pathway and gives rise to a long-lived (3)MLCT state similar in nature to that seen in [Ru(phen)3](2+). Using NMR, the equilibrium constant for the hydration reaction of 1 in acetonitrile was determined to be 0.0253. From this data and experimental fitting of the luminescent titration data, the equilibrium constant for 2 of 1.62 × 10(-5) and emission yields for hydrated 1 and 2 were determined. Interestingly, all three quinone functions must be hydrated in 2 for luminescence, which is why the equilibrium constants vary so much. The 'turn on' luminescence allows for a very sensitive detection of water in aprotic solvents such as acetonitrile.

  17. COMPARISON OF IMMUNOASSAY AND GAS CHROMATOGRAPHY/MASS SPECTROMETRY METHODS FOR MEASURING 3,5,6-TRICHLORO-2PYRIDINOL IN MULTIPLE SAMPLE MEDIA

    EPA Science Inventory

    Two enzyme-linked immunosorbent assay (ELISA) methods were evaluated for the determination of 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) in multiple sample media (dust, soil, food, and urine). The dust and soil samples were analyzed by a commercial RaPID immunoassay testing kit. ...

  18. Photolytic, thermal, addition, and cycloaddition reactions of 2-diazo-5,6- and -3,8-disubstituted acenaphthenones.

    PubMed

    Blair, Patricia A; Chang, Sou-Jen; Shechter, Harold

    2004-10-15

    Preparation and varied thermal and photolytic reactions of 2-diazo-5,6-(disubstituted)acenaphthenones (11a-d) and 2-diazo-3,8-dimethoxyacenaphthenone (12) are reported. Alcohols react thermally and photolytically with 11a-c with losses of N(2) to yield 2-alkoxynaphthenones (24a,band 47a,b) and acenaphthenones (25 and 48a,b). Aniline and diphenylamine are converted by 11a-c at 180 degrees C to acenaph[1,2-b]indoles (29a,b and 53a,b). Thermolyses of 11a-c at approximately 450 degrees C (0.15 mmHg) yield reduction products 25 and 48a,b, respectively. Wolff rearrangements to 1,8-naphthyleneketenes (15a-d) and/or their derivatives are not observed in the above experiments. Oxygen converts 11a-c thermally to acenaphthenequinones (19a-c) and/or 1,8-naphthalic anhydrides. Insertion, addition, substitution, and/or isomerization reactions occur upon irradiation of 2-diazoacenaphthenones in cyclohexane, benzene, and tetrahydrofuran. Photolysis of 11d in benzene in the presence of O(2) yields the insertion-oxidation product 2-hydroxy-5,6-dinitro-2-phenylacenaphthenone (60). Photolyses of 11a-c in nitriles result in N(2) evolution and dipolar cycloaddition to give acenaph[1,2-d]oxazoles (41 and 61a,b). Acetylenes undergo thermal and photolytic cycloaddition/1,5-sigmatropic rearrangement reactions with 11a-d with N(2) retention to give pyrazolo[5,1-a]quinolin-7-ones (69f-j). 2-Diazoacenaphthenones 1a and 11a react thermally and photolytically with electronegatively-substituted olefins with N(2) expulsion to yield (E)- and (Z)-2-oxospiro[acenaphthylene-1(2H),1'cyclopropanes] 73a-c and 74a-c, respectively. The mechanisms of the reactions of 1a, 11a-d, and 12 reported are discussed.

  19. Higher specificity of nucleic acid sequence-based amplification isothermal technology than of real-time PCR for quantification of HIV-1 RNA on dried blood spots.

    PubMed

    Mercier-Delarue, Severine; Vray, Muriel; Plantier, Jean Christophe; Maillard, Theodora; Adjout, Zidan; de Olivera, Fabienne; Schnepf, Nathalie; Maylin, Sarah; Simon, Francois; Delaugerre, Constance

    2014-01-01

    Dried blood spots (DBS) are widely proposed as a plasma surrogate for monitoring antiretroviral treatment efficacy based on the HIV-1 RNA level (viral load [VL]) in resource-limited settings. Interfering coamplification of cell-associated HIV-1 DNA during reverse transcription (RT)-PCR can be avoided by using nucleic acid sequence-based amplification (NASBA) technology, which is based on an RNA template and isothermic conditions. We analyzed VL values obtained with DBS and plasma samples by comparing isothermic NASBA (NucliSENS EasyQ HIV-1 V2.0; bioMérieux) with real-time RT-PCR (Cobas TaqMan HIV-1 V2.0; Roche). Samples from 197 HIV-1-infected patients were tested (non-B subtypes in 51% of the cases). Nucleic acid extractions were performed by use of NucliSENS EasyMAG (bioMérieux) and Cobas AmpliPrep (Roche) before the NASBA and RT-PCR quantifications, respectively. Both quantification assays have lower limits of detection of 20 (1.3) and 800 (2.9) log10 copies/ml (log) in plasma and DBS, respectively. The mean (DBS minus plasma) differences were -0.39 and -0.46 log, respectively, for RT-PCR and NASBA. RT-PCR on DBS identified virological failure in 122 of 126 patients (sensitivity, 97%) and viral suppression in 58 of 70 patients (specificity, 83%), yielding 12 false-positive results (median, 3.2 log). NASBA on DBS identified virological failure in 85 of 96 patients (sensitivity, 89%) and viral suppression in 95 of 97 patients (specificity, 98%) and yielded 2 false-positive results (3.0 log for both). Both technologies detected HIV-1 RNA in DBS at a threshold of 800 copies/ml. This higher specificity of NASBA technology could avoid overestimation of poor compliance or the emergence of resistance when monitoring antiretroviral efficacy with the DBS method.

  20. Finite-fault slip model of the 2011 Mw 5.6 Prague, Oklahoma earthquake from regional waveforms

    USGS Publications Warehouse

    Sun, Xiaodan; Hartzell, Stephen

    2014-01-01

    The slip model for the 2011 Mw 5.6 Prague, Oklahoma, earthquake is inferred using a linear least squares methodology. Waveforms of six aftershocks recorded at 21 regional stations are used as empirical Green's functions (EGFs). The solution indicates two large slip patches: one located around the hypocenter with a depth range of 3–5.5 km; the other located to the southwest of the epicenter with a depth range from 7.5 to 9.5 km. The total moment of the solution is estimated at 3.37 × 1024 dyne cm (Mw 5.65). The peak slip and average stress drop for the source at the hypocenter are 70 cm and 90 bars, respectively, approximately one half the values for the Mw 5.8 2011 Mineral, Virginia, earthquake. The stress drop averaged over all areas of slip is 16 bars. The relatively low peak slip and stress drop may indicate an induced component in the origin of the Prague earthquake from deep fluid injection.

  1. The 5-6 December 1991 FIRE IFO II jet stream cirrus case study: Possible influences of Volcanic Aerosols

    NASA Technical Reports Server (NTRS)

    Sassen, Kenneth; Starr, David O'C.; Mace, Gerald G.; Poellot, Michael R.; Melfi, S. H.; Eberhard, Wynn L.; Spinhirne, James D.; Eloranta, E. W.; Hagen, Donald E.; Hallett, John

    1995-01-01

    In presenting an overview of the cirus clouds comprehensively studied by ground-based and airborne sensors from Coffeyville, Kansas, during the 5-6 December 1992 Project First ISCCP Region Experiment (FIRE) Intensive Fields Observation (IFO) II case study period, evidence is provided that volcanic aerosols friom the June 1991 Pinatubo eruptions may have significantly influenced the formation and maintenance of the cirrus. Following the local appearance of a spur of stratospheric volcanic debris from the subtropics, a series of jet streaks subsequently conditioned the troposphere through tropopause foldings with sulfur-based particles that became effective cloud-forming nuclei in cirrus clouds. Aerosol and ozone measurements suggest a complicated history of stratospheric-tropospheric exchanges embedded within the upper-level flow, and cirrus cloud formation was noted to occur locally at the boundaries of stratospheric aerosol-enriched layers that became humidified through diffusion, precipitation, or advective processes. Apparent cirrus cloud alterations include abnormally high ice crystal concentrations (up to approximately 600/L), complex radial ice crystal types, and relatively large haze particles in cirrus uncinus cell heads at temperatures between -40 and -50 C. Implications for volcanic-cirrus cloud climate effects and usual (nonvolcanic aerosol) jet stream cirrus cloud formation are discussed.

  2. The 5-6 December 1991 FIRE IFO 2 jet stream cirrus case study: The influence of volcanic aerosols

    NASA Technical Reports Server (NTRS)

    Sassen, Kenneth; Mace, Gerald G.; Starr, David; Poellot, Michael R.; Melfi, S. H.; Eberhard, Wynn L.; Spinhirne, James D.; Eloranta, E. W.; Hagen, Donald E.; Hallett, John

    1993-01-01

    In presenting an overview of the cirrus clouds comprehensively studied by ground-based and airborne sensors from Coffeyville, KS, during the 5-6 Dec. 1992 Project FIRE (First International Satellite Cloud Climatology Project Regional Experiment) IFO II case study period, evidence is provided that volcanic aerosols from the June 1991 Pinatubo eruptions significantly influenced the formation and maintenance of the cirrus. Following the local appearance of a spur of stratospheric volcanic debris from the subtropics, a series of jet streaks subsequently conditioned the troposphere through tropopause foldings with sulfur-based particles that became effective cirrus cloud-forming nuclei. Aerosol and ozone measurements suggest a complicated history of stratospheric-tropospheric exchanges embedded within the upper level flow, and cirrus cloud formation was noted to occur locally at the boundaries of stratospheric aerosol-enriched layers that became humidified through diffusion, precipitation, or advective processes. Apparent cirrus cloud alterations include abnormally high ice crystal concentrations (up to approximately 600 l(sup -1), small but complex radial ice crystal types, and relatively large haze particles in cirrus uncinus cell heads at temperatures between -40 to -50 C. Implications for volcanic-cirrus cloud climate effects, and usual (non-volcanic aerosol) jet stream cirrus cloud formation are discussed.

  3. Thermodynamic relationship between structural isomers of the thermochromic compound bis(N-Isopropyl-5,6-benzosalicylideneiminato)nickel(II).

    PubMed

    Wang, Qi; Takeuchi, Akira; Yamamura, Yasuhisa; Saito, Kazuya; Mori, Wasuke; Sorai, Michio

    2008-09-04

    A pair of structural isomers was isolated at room temperature for the thermochromic nickel complex bis( N-isopropyl-5,6-benzosalicylideneiminato)nickel(II); one is a diamagnetic green form with square-planar coordination geometry (G phase), and the other is a paramagnetic brown form with a tetrahedral geometry (B phase). However, a question as to which form is thermodynamically stable was left open. To solve this problem, thermal and magnetic properties of this complex were investigated by adiabatic heat capacity calorimetry in the 6-508 K temperature range and magnetic measurements in the 2-400 K region. In addition to the two forms previously reported, two metastable crystal forms (G' and B' phases) were found. The stable phase sequence was G phase, B phase, and then liquid upon heating. The supercooled B phase gave rise to a small phase transition with nonmagnetic origin at around 50 K. By rapidly cooling the liquid, a glassy liquid state was realized below approximately 290 K. The order of thermodynamic stability at 298.15 K was revealed to be the G, B, G', and then the B' phase. The entropy, enthalpy, and Gibbs energy differences between the B and the G phases at 298.15 K were S degrees (B) - S degrees (G) = 32.8 J K (-1) mol (-1), H degrees (B) - H degrees (G) = 16.0 kJ mol (-1), and G degrees (B) - G degrees (G) = 6.25 kJ mol (-1), respectively.

  4. 5-Fluorouracil catabolism to 5-fluoro-5,6-dihydrouracil is reduced by acute liver impairment in mice

    SciTech Connect

    Innocenti, Federico; Danesi, Romano; Bocci, Guido; Natale, Gianfranco . E-mail: gianfranco.natale@anist.med.unipi.it; Del Tacca, Mario

    2005-03-01

    This study investigated the effect of acute liver damage on the inactivation of 5-fluorouracil (5-FU) to its main catabolite 5-fluoro-5,6-dihydrouracil (5-FUH{sub 2}) in mice. Plasma pharmacokinetics of 5-FU and 5-FUH{sub 2} in mice receiving 5-FU (10, 30, and 90 mg/kg) were compared to those in mice pretreated with carbon tetrachloride and receiving the same 5-FU doses. Carbon tetrachloride-induced hepatic damage was histopathologically examined under light microscopy and serum transaminases and dihydropyrimidine dehydrogenase activities were also measured. Liver histopathology and elevated aminotransferase activity levels confirmed the presence of liver damage. 5-FU C{sub max} and AUC both increased up to 71% in mice with liver damage. This was reflected by decreased 5-FUH{sub 2} production, since 5-FUH{sub 2} C{sub max} and AUC levels decreased up to 47% and 61%, respectively. Metabolic ratios between 5-FUH{sub 2} and 5-FU AUCs were considerably decreased as well, further suggesting that liver damage caused a reduction in 5-FU catabolism. DPD activity was not altered in damaged livers. The present results indicate that 5-FU disposition in mice could be profoundly altered in the presence of severe liver impairment, potentially leading to enhanced anabolic activation of 5-FU. This effect seems to be ascribed to a reduction of viable hepatocytes, rather than to an inactivation of DPD activity.

  5. The 5-6 December 1991 FIRE IFO 2 Jet Stream Cirrus Case Study: Possible Influences of Volcanic Aerosols

    NASA Technical Reports Server (NTRS)

    Sassen, Kenneth; Starr, David OC.; Mace, Gerald G.; Poellot, Michael R.; Melfi, S. H.; Eberhard, Wynn L.; Spinhirne, James D.; Eloranta, E. W.; Hagen, Donald E.; Hallett, John

    1996-01-01

    In presenting an overview of the cirrus clouds comprehensively studied by ground based and airborne sensors from Coffeyville, Kansas, during the 5-6 December 1992 First ISCCP Regional Experiment (FIRE) intensive field observation (IFO) case study period, evidence is provided that volcanic aerosols from the June 1991 Pinatubo eruptions may have significantly influenced the formation and maintenance of the cirrus. Following the local appearance of a spur of stratospheric volcanic debris from the subtropics, a series of jet streaks subsequently conditioned the troposphere through tropopause foldings with sulfur based particles that became effective cloud forming nuclei in cirrus clouds. Aerosol and ozone measurements suggest a complicated history of stratospheric-tropospheric exchanges embedded with the upper level flow, and cirrus cloud formation was noted to occur locally at the boundaries of stratospheric aerosol enriched layers that became humidified through diffusion, precipitation, or advective processes. Apparent cirrus cloud alterations include abnormally high ice crystal concentrations (up to approximately 600 L(exp. 1)), complex radial ice crystal types, and relatively large haze particles in cirrus uncinus cell heads at temperatures between -40 and -50 degrees C. Implications for volcanic-cirrus cloud climate effects and unusual (nonvolcanic) aerosol jet stream cirrus cloud formation are discussed.

  6. 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.

  7. Fluorophotometric determination of histone with 3,4,5,6-tetrafluoro-2-carboxyphenylfluorone-manganese(II) complex and its characterization.

    PubMed

    Miyachi, Kanako; Hoshino, Mitsuru; Kadobayashi, Hiroko; Moriyama, Kenzo; Asano, Mamiko; Yamaguchi, Takako; Fujita, Yoshikazu

    2013-01-01

    A simple fluorophotometric method for the determination of histone has been developed. This method involves a fluorescence quenching reaction that results in the formation of a complex of manganese(II), 3,4,5,6-tetrafluoro-2-carboxyphenylfluorone (TFCPF), and histone in a non-ionic surfactant micellar medium. The calibration curve was found to be linear in the range of 0.5 to 2.0 µg/mL. The binding parameters (n, number of binding sites; K, binding constant) and thermodynamic parameters (ΔG(0), change in Gibbs free energy; ΔH(0), change in enthalpy; ΔS(0), change in entropy) were investigated spectrophotometrically for the elucidation of the reaction mechanism. The resulting binding parameters (n=4.08 and K=3.16×10(4) m(-1) at 25°C) and thermodynamic parameters (ΔG=-25.83 kJ/mol, ΔH=-9.83 kJ/mol, and ΔS=53.68 J/(mol K)) suggest that the colored complex in this reaction system is an ion-association complex between manganese(II)-TFCPF and histone.

  8. Acid-coated Textiles (pH 5.5-6.5)--a New Therapeutic Strategy for Atopic Eczema?

    PubMed

    Jaeger, Teresa; Rothmaier, Markus; Zander, Holger; Ring, Johannes; Gutermuth, Jan; Anliker, Mark D

    2015-07-01

    Increased transepidermal water loss (TEWL) and decreased skin capacitance are characteristic features of the disturbed epidermal barrier in atopic eczema (AE). The "acid mantle", which is a slightly acidic film on the surface of the skin has led to the development of acidic emollients for skin care. In this context, the effect of citric acid-coated textiles on atopic skin has not been examined to date. A textile carrier composed of cellulose fibres was coated with a citric acid surface layer by esterification, ensuring a constant pH of 5.5-6.5. Twenty patients with AE or atopic diathesis were enrolled in the study. In a double-blind, half-side experiment, patients had to wear these textiles for 12 h a day for 14 days. On day 0 (baseline), 7 and 14, tolerability (erythema, pruritus, eczema, wearing comfort) and efficacy on skin barrier were assessed by TEWL skin hydration (corneometry/capacitance), pH and clinical scoring of eczema (SCORAD). Citric acid-coated textiles were well tolerated and improved eczema and objective parameters of skin physiology, including barrier function and a reduced skin surface pH, with potential lower pathogenic microbial colonisation.

  9. Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis suggests functions in distinct chromosome processes.

    PubMed

    Gómez, Rocío; Jordan, Philip W; Viera, Alberto; Alsheimer, Manfred; Fukuda, Tomoyuki; Jessberger, Rolf; Llano, Elena; Pendás, Alberto M; Handel, Mary Ann; Suja, José A

    2013-09-15

    Four members of the structural maintenance of chromosome (SMC) protein family have essential functions in chromosome condensation (SMC2/4) and sister-chromatid cohesion (SMC1/3). The SMC5/6 complex has been implicated in chromosome replication, DNA repair and chromosome segregation in somatic cells, but its possible functions during mammalian meiosis are unknown. Here, we show in mouse spermatocytes that SMC5 and SMC6 are located at the central region of the synaptonemal complex from zygotene until diplotene. During late diplotene both proteins load to the chromocenters, where they colocalize with DNA Topoisomerase IIα, and then accumulate at the inner domain of the centromeres during the first and second meiotic divisions. Interestingly, SMC6 and DNA Topoisomerase IIα colocalize at stretched strands that join kinetochores during the metaphase II to anaphase II transition, and both are observed on stretched lagging chromosomes at anaphase II following treatment with Etoposide. During mitosis, SMC6 and DNA Topoisomerase IIα colocalize at the centromeres and chromatid axes. Our results are consistent with the participation of SMC5 and SMC6 in homologous chromosome synapsis during prophase I, chromosome and centromere structure during meiosis I and mitosis and, with DNA Topoisomerase IIα, in regulating centromere cohesion during meiosis II.

  10. Finite-fault slip model of the 2011 Mw 5.6 Prague, Oklahoma earthquake from regional waveforms

    NASA Astrophysics Data System (ADS)

    Sun, Xiaodan; Hartzell, Stephen

    2014-06-01

    The slip model for the 2011 Mw 5.6 Prague, Oklahoma, earthquake is inferred using a linear least squares methodology. Waveforms of six aftershocks recorded at 21 regional stations are used as empirical Green's functions (EGFs). The solution indicates two large slip patches: one located around the hypocenter with a depth range of 3-5.5 km; the other located to the southwest of the epicenter with a depth range from 7.5 to 9.5 km. The total moment of the solution is estimated at 3.37 × 1024 dyne cm (Mw 5.65). The peak slip and average stress drop for the source at the hypocenter are 70 cm and 90 bars, respectively, approximately one half the values for the Mw 5.8 2011 Mineral, Virginia, earthquake. The stress drop averaged over all areas of slip is 16 bars. The relatively low peak slip and stress drop may indicate an induced component in the origin of the Prague earthquake from deep fluid injection.

  11. Effect of gemini (alkanediyl-α,ω-bis(dimethylcetylammonium bromide)) (16-s-16, s=4, 5, 6) surfactants on the interaction of ninhydrin with chromium-glycylphenylalanine.

    PubMed

    Kumar, Dileep; Rub, Malik Abdul; Akram, Mohd; Kabir-ud-Din

    2014-11-11

    The effect of gemini (alkanediyl-α,ω-bis(dimethylcetylammonium bromide)) (16-s-16, s=4, 5, 6) surfactants on the interaction of ninhydrin with chromium(III) complex of glycylphenylalanine ([Cr(III)-Gly-Phe]2+) has been investigated using UV-visible spectrophotometer at different temperatures. The order of reaction with respect to [Cr(III)-Gly-Phe]2+ is unity while it is fractional with respect to ninhydrin. Whereas, the values of rate constant (kψ) increase and leveling-off regions, like conventional single chain cetyltrimethylammonium bromide (CTAB) surfactant, were observed with geminis, later produces a third region of increasing kψ at higher gemini surfactant concentrations. This unusual third-region effect of the gemini micelles is assigned to changes in their micellar morphologies. The results obtained in micellar media were treated in terms of pseudo-phase model. The values of thermodynamic parameters (Ea, ΔH# and ΔS#) and binding constants (KA and KNin) have been evaluated.

  12. We are Family: the Conformations of 1-FLUOROALKANES, C_nH2n+1F (n = 2,3,4,5,6,7,8)

    NASA Astrophysics Data System (ADS)

    Obenchain, Daniel A.; Orellana, W.; Cooke, S. A.

    2016-06-01

    he pure rotational spectra of the n = 5, 6, 7, and 8 members of the 1-fluoroalkane family have been recorded between 7 GHz and 14 GHz using chirped pulse Fourier transform microwave spectroscopy. The spectra have been analyzed and results will be presented and compared with previous work on the n= 2, 3, and 4 members. The lowest energy conformer for all family members has the common feature that the fluorine is in a gauche position relative to the alkyl tail for which all other heavy atom dihedral angles, where appropriate, are 180 degrees. For the n = 3 and higher family members the second lowest energy conformer has all heavy atom dihedral angles equal to 180 degrees. For each family member transitions carried by both low energy conformers were observed in the collected rotational spectra. Quantum chemical calculations were performed and trends in the energy separations between these two common conformers will be presented as a function of chain length. Furthermore, longer chain lengths have been examined using only quantum chemical calculations and results will be presented. M. Hayashi, M. Fujitake, T. Inagusa, S. Miyazaki, J.Mol.Struct., 216, 9-26, 1990 W. Caminati, A. C. Fantoni, F. Manescalchi, F. Scappini, Mol.Phys., 64, 1089 ,1988 L. B. Favero, A. Maris, A. Degli Esposti, P. G. Favero, W. Caminati, G. Pawelke, Chem.Eur.J., 6(16), 3018-3025, 2000

  13. Hepatotoxicity and nephrotoxicity induced by the chlorpyrifos and chlorpyrifos-methyl metabolite, 3,5,6-trichloro-2-pyridinol, in orally exposed mice.

    PubMed

    Deng, Yongfeng; Zhang, Yan; Lu, Yifeng; Zhao, Yanping; Ren, Hongqiang

    2016-02-15

    3,5,6-Trichloro-2-pyridinol (TCP) is a primary degradation product of chlorpyrifos and chlorpyrifos-methyl. TCP has longer half-life in soil and greater solubility in water than its parent compound, and cause wide contamination in environments. However, studies about the toxic effects of TCP are limited and outdate. In this study, 5 mg/kg/day, 50 mg/kg/day, and 150 mg/kg/day TCP were given to male mice through gavage for four weeks. As a result, the final body weights of TCP treated groups were significantly lower than control, and the relative organ weights of the liver and kidney were significantly higher than that of control. In addition, NMR-based metabolomics was used to investigate the toxic effects of TCP. It was found that a total of 39 serum metabolites were significantly changed in the TCP-treated groups, and these metabolites are related to hepatotoxicity and nephrotoxicity. These results were also confirmed by histopathology, serum biochemical, and oxidative stress analysis. In addition, metabolic disturbances due to TCP exposure were also observed based on altered metabolites. As far as we know, these results are the first to show the metabolomic toxicity of TCP, which warrants further research.

  14. Efficient red emission from PMMA films doped with 5,6-DTFI europium(III) complexes: synthesis, structure and photophysical properties.

    PubMed

    Li, Weizuo; Yan, Pengfei; Hou, Guangfeng; Li, Hongfeng; Li, Guangming

    2013-08-28

    A new β-diketone, 5,6-dimethoxy-2(2,2,2-trifluoroethyl)-1-indone (5,6-DTFI), has been designed and synthesized. Two series of four 5,6-DTFI Sm(3+) and Eu(3+) complexes, namely, Eu(5,6-DTFI)3(H2O)2 (1), Eu(5,6-DTFI)3(Phen) (2), Sm(5,6-DTFI)3(H2O)2 (3) and Sm(5,6-DTFI)3(Phen) (4) (Phen = 1,10-phenanthroline), have been isolated. X-ray diffraction analysis reveals that all complexes 1-4 are of mononuclear structures. Luminescent and phosphorescent spectra of complexes 1-4 show strong characteristic emissions of the corresponding Eu(3+) and Sm(3+) ions. Upon complexes 1 and 2 were doped into the poly(methylmethacrylate) (PMMA) forming the films, the PMMA polymer matrix acting as a co-sensitizer for Eu(3+) ion enhances the luminescent lifetimes, overall quantum yields and the thermal stability in comparison with the precursor complexes.

  15. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Gregory, Dennis E.

    Decisions made by federal and state courts during 1983 concerning higher education are reported in this chapter. Issues of employment and the treatment of students underlay the bulk of the litigation. Specific topics addressed in these and other cases included federal authority to enforce regulations against age discrimination and to revoke an…

  16. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    Litigation in 1987 was very brisk with an increase in the number of higher education cases reviewed. Cases discussed in this chapter are organized under four major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining and denial of employee benefits; (3)…

  17. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Finnegan, Dorothy E.

    The higher education case law in 1988 is extensive. Cases discussed in this chapter are organized under five major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining, and denial of employee benefits; (3) students, involving admissions, financial aid, First…

  18. Higher Education.

    ERIC Educational Resources Information Center

    Knowles, Laurence W.; Wedlock, Eldon D., Jr.

    Courts have been consistently reluctant to interfere with governing boards' powers to control the administration of institutions of higher education. This deference seems to be based on the belief that board expertise makes it significantly more qualified than are the courts to make the necessary administrative decisions. Uncritical deference by…

  19. FOCUSING COSMIC TELESCOPES: EXPLORING REDSHIFT z approx 5-6 GALAXIES WITH THE BULLET CLUSTER 1E0657 - 56

    SciTech Connect

    Bradac, Marusa; Treu, Tommaso; Marshall, Phil; Applegate, Douglas; Gonzalez, Anthony H.; Clowe, Douglas; Forman, William; Jones, Christine; Schneider, Peter; Zaritsky, Dennis

    2009-12-01

    The gravitational potential of clusters of galaxies acts as a cosmic telescope allowing us to find and study galaxies at fainter limits than otherwise possible and thus probe closer to the epoch of formation of the first galaxies. We use the Bullet cluster 1E0657 - 56 (z = 0.296) as a case study, because its high mass and merging configuration makes it one of the most efficient cosmic telescopes we know. We develop a new algorithm to reconstruct the gravitational potential of the Bullet cluster based on a non-uniform adaptive grid, combining strong and weak gravitational lensing data derived from deep Hubble Space Telescope/Advanced Camera for Surveys F606W-F775W-F850LP and ground-based imaging. We exploit this improved mass map to study z approx 5-6 Lyman break galaxies (LBGs), which we detect as dropouts. One of the LBGs is multiply imaged, providing a geometric confirmation of its high redshift, and is used to further improve our mass model. We quantify the uncertainties in the magnification map reconstruction in the intrinsic source luminosity, and in the volume surveyed, and show that they are negligible compared to sample variance when determining the luminosity function of high-redshift galaxies. With shallower and comparable magnitude limits to Hubble Ultra Deep Field (HUDF) and Great Observatories Origins Deep Survey (GOODS), the Bullet cluster observations, after correcting for magnification, probe deeper into the luminosity function of the high-redshift galaxies than GOODS and only slightly shallower than HUDF. We conclude that accurately focused cosmic telescopes are the most efficient way to sample the bright end of the luminosity function of high-redshift galaxies and-in case they are multiply imaged-confirm their redshifts.

  20. Spectrophotometric determination of fluoxetine and sertraline using chloranil, 2, 3 dichloro-5, 6 dicyano benzoquinone and iodine.

    PubMed

    Bebawy, L I; El-Kousy, N; Suddik, J K; Shokry, M

    1999-10-01

    Spectrophotometric procedures are presented for the determination of two commonly used antidepressant drugs, fluoxetine (I) and sertraline hydrochloride (II). The methods are based mainly on charge transfer complexation reaction of these drugs with either pi acceptors chloranil and 2, 3 dichloro-5, 6-dicyanoquinone (DDQ) or sigma acceptor iodine. The colored products are quantified spectrophotometrically at 550, 450 and 263 nm for fluoxetine and at 450, 455 and 290 nm for sertraline in chloranil, DDQ and iodine methods, respectively. The molar combining ratio and the optimum assay conditions were studied. The methods determine the cited drugs in concentration ranges of 8-640, 16-112 and 7.5-60 microg/ml with mean percentage recoveries of 99.83, 99.76 and 100.00% and R.S.D. of 1.24, 0.95 and 1.13% in fluoxetine and ranges of 16-160, 15-105 and 6-48 microg/ml with mean percentage recoveries of 100.39, 99.78 and 99.69% and R.S.D. of 1.02, 0.81 and 0.57% in sertraline for chloranil, DDQ and iodine methods, respectively. A more detailed investigation of the complex formed was made with respect to its composition, association constant K(AD)c, molar absorptivity xiAD(A) and free energy change deltaG. The proposed methods were applied successfully to the determination of the cited drugs either in pure or dosage forms with good accuracy and precision. The results were compared statistically with those given by the reported methods.

  1. Three-dimensional evaluation of facial morphology in children aged 5-6 years with a Class III malocclusion.

    PubMed

    Krneta, Bojana; Primožič, Jasmina; Zhurov, Alexei; Richmond, Stephen; Ovsenik, Maja

    2014-04-01

    The aim of this study was to evaluate facial morphology in 25 Class III and 46 non-Class III children aged 5-6 years using three-dimensional (3D) laser imaging; 3D facial images were obtained, two average facial templates were constructed for the non-Class III male and female groups, each individual face was superimposed on the corresponding average template and group comparisons were evaluated (facial height, facial convexity, mandibular position and facial surface morphology). Differences between parameters were evaluated by using an analysis of variance and colour deviation maps. The results showed that Class III children had less mid-face prominence and a concave facial profile when compared to non-Class III children (P = 0.002 and P = 0.018). The position of the pg point in the z-axis just failed to reach statistical significance when comparing the two groups (P = 0.051). A vertical analysis showed no statistical significance between the groups, when evaluating middle (n-sn) and lower (sn-pg) facial height. Coincidence of the Class III faces to normal templates with a tolerance set as 0.5 mm was low (less than 30%). The soft tissue characteristics of a Class III face differ significantly from the non-Class III face in the mid-face region and in the facial profile. A 3D laser imaging method evaluated and identified morphological characteristics of Class III children in deciduous dentition, which could in the future become an important diagnostic tool in small children. The most important clinical advantage of this study is the non-invasiveness of the method.

  2. Synthesis, antimicrobial activity and QSAR studies of new 2,3-disubstituted-3,3a,4,5,6,7-hexahydro-2H-indazoles.

    PubMed

    Minu, Maninder; Thangadurai, Ananda; Wakode, Sharad Ramesh; Agrawal, Shyam Sundar; Narasimhan, Balasubramanian

    2009-06-01

    Antimicrobial activity of synthesized 2,3-disubstituted-3,3a,4,5,6,7-hexahydro-2H-indazole derivatives indicated that 3-(4-chlorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (6) and 3-(4-fluorophenyl)-2-(4-nitrophenylsulfonyl)-3,3a,4,5,6,7-hexahydro-2H-indazole (20) were the most active compounds. Further, the results of QSAR studies indicated the importance of topological parameters (2)chi and (2)chi(v) in defining the antimicrobial activity of hexahydroindazoles.

  3. Reconciling icetexane biosynthetic connections with their chemical synthesis: total synthesis of (+/-)-5,6-dihydro-6alpha-hydroxysalviasperanol, (+/-)-brussonol, and (+/-)-abrotanone.

    PubMed

    Simmons, Eric M; Yen, Jennifer R; Sarpong, Richmond

    2007-07-05

    A unified strategy for the chemical synthesis of the icetexane diterpenoids brussonol and 5,6-dihydro-6alpha-hydroxysalviasperanol has led to a structural revision of the recently isolated natural products abrotandiol and abrotanone.

  4. Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.

    PubMed

    Páleníček, Tomáš; Lhotková, Eva; Žídková, Monika; Balíková, Marie; Kuchař, Martin; Himl, Michal; Mikšátková, Petra; Čegan, Martin; Valeš, Karel; Tylš, Filip; Horsley, Rachel R

    2016-08-01

    MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats. Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30min and almost returned to zero 6h after subcutaneous (sc.) administration of 10mg/kg MDAI; brain/serum ratio was ~4. MDAI particularly accumulated in lung tissue. In the open field, MDAI (5, 10, 20 and 40mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60min after treatment. Unexpectedly, 40mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33mg/kg sc. and 35mg/kg intravenous but was not established up to 40mg/kg after gastric administration. Disseminated intravascular coagulopathy (DIC) with brain oedema was concluded as a direct cause of death in sc. treated animals. Finally, MDAI (10, 20mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3

  5. Synthesis, conformation, and dopaminergic activity of 5,6-ethano-bridged derivatives of selective dopaminergic 3-benzazepines.

    PubMed

    Weinstock, J; Oh, H J; DeBrosse, C W; Eggleston, D S; Wise, M; Flaim, K E; Gessner, G W; Sawyer, J L; Kaiser, C

    1987-08-01

    To probe the suggestion that D-1 (DA1) dopamine receptors might possess an accessory pi-binding site in a location complementary to a suitably oriented aromatic ring (i.e., in an axial orientation approximately orthogonal to the catechol nucleus) in agonists such as 2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine-7,8-diol (1) and 3',4'-dihydroxynomifensine (2) that are selective for this subtype, cis- and trans-2,3,4,8,9,9a-hexahydro-4-phenyl-1H-indeno[1,7-cd]azepine-6,7-diol were prepared. These compounds are 5,6-ethano-bridged derivatives of the D-1 selective dopamine receptor agonist 1. Introduction of the bridge reduces the conformational mobility of the parent molecule. Comprehensive conformational analyses by molecular mechanical methods indicated that both the cis and trans isomers could attain a conformation that places the phenyl substituent in an axial orientation. X-ray analysis of the trans isomer showed an axial disposition of the phenyl ring; however, NMR studies suggest that this conformation is fixed in the trans isomer, but not in the cis. The dopamine receptor binding affinity and intrinsic activity of the cis isomer were considerably greater than those of its trans counterpart; the cis isomer also demonstrated a high degree of selectivity for the D-1 subtypes. One possible explanation of these results, suggested by the molecular modeling studies, is that both the axial orientation of the phenyl postulated to be required for binding to the receptor and a putatively requisite location of the nitrogen in approximately the plane of the catechol ring can be attained only by the cis isomer in which the tetrahydroazepine ring is in a twist conformation. Conversely, these results might simply suggest a preference of the D-1 receptors for benzazepine agonists having the phenyl group in an equatorial orientation. Still another possibility is that the D-1 receptor binding site is in a sterically hindered area accessible only to compounds that are relatively

  6. Accumulation of 14C-5,6-dihydroxytryptamine-melanin in intrathecal and subependymal phagocytes of the rat CNS and possible routes of their elimination from brain

    SciTech Connect

    Baumgarten, H.G.; Moritz, F.; Schlossberger, H.G.

    1981-01-01

    14C-5,6-DHT-Melanin, a labelled synthetic polymer resembling the naturally occurring melanin formed in brain by autoxidation of dopamine, was injected into the left lateral ventricle of adult rats, and its fate followed by autoradiography and by transmission electron microscopy of structures identified as labelled in preceding light micrographs, and by EM-autoradiography. Shortly after injection, melanin particles (easily identified in the em because of their size, structure and electron opacity) were seen ingested by supraependymal and epiplexus cells, by cells residing in the piaarachnoid, i.e. free subarachnoidal cells and perivascular cells, and by subependymally located microglia-like cells with intraventricular processes. Up to day four, an increase in the number of labelled phagocytes in the CSF was noted which transformed into typical reactive macrophages. Beyond this time, many intraventricular melanin-loaded phagocytes formed rounded clusters; cells of such clusters were subsequently found to invade the brain parenchyma by penetrating the ependymal lining and to accumulate in the perivascular space of brain vessels. 14C-Melanin-storing macrophages were found in the marginal sinus of the deep jugular lymph nodes suggesting emigration of CNS-derived phagocytes via lymphatics or prelymphatics that contact the subarachnoidal space compartment. This does not exclude the possibility that some of the macrophages leave the brain via the systemic circulation by penetrating the vascular endothelium; these may be disposed of in peripheral organs other than the lymph nodes.

  7. Charge-transfer complexes of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with amino molecules in polar solvents

    NASA Astrophysics Data System (ADS)

    Berto, Silvia; Chiavazza, Enrico; Ribotta, Valentina; Daniele, Pier Giuseppe; Barolo, Claudia; Giacomino, Agnese; Vione, Davide; Malandrino, Mery

    2015-10-01

    The charge-transfer complexes have scientific relevance because this type of molecular interaction is at the basis of the activity of pharmacological compounds and because the absorption bands of the complexes can be used for the quantification of electron donor molecules. This work aims to assess the stability of the charge-transfer complexes between the electron acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and two drugs, procaine and atenolol, in acetonitrile and ethanol. The stability of DDQ in solution and the time required to obtain the maximum complex formation were evaluated. The stoichiometry and the stability of the complexes were determined, respectively, by Job's plot method and by the elaboration of UV-vis titrations data. The latter task was carried out by using the non-linear global analysis approach to determine the equilibrium constants. This approach to data elaboration allowed us to overcome the disadvantages of the classical linear-regression method, to obtain reliable values of the association constants and to calculate the entire spectra of the complexes. NMR spectra were recorded to identify the portion of the donor molecule that was involved in the interaction. The data support the participation of the aliphatic amino groups in complex formation and exclude the involvement of the aromatic amine present in the procaine molecule.

  8. Structural Polymorphism and Thin Film Transistor Behavior in the Fullerene Framework Molecule 5,6;11,12-di-o-Phenylenetetracene.

    PubMed

    Wombacher, Tobias; Gassmann, Andrea; Foro, Sabine; von Seggern, Heinz; Schneider, Jörg J

    2016-05-10

    The molecular structure of the hydrocarbon 5,6;11,12-di-o-phenylenetetracene (DOPT), its material characterization and evaluation of electronic properties is reported for the first time. A single-crystal X-ray study reveals two different motifs of intramolecular overlap with herringbone-type arrangement displaying either face-to-edge or co-facial face-to-face packing depicting intensive π-π interactions. Density functional theory (DFT) calculations underpin that a favorable electronic transport mechanism occurs by a charge hopping process due to a π-bond overlap in the DOPT polymorph with co-facial arene orientation. The performance of polycrystalline DOPT films as active organic semiconducting layer in a state-of-the-art organic field effect transistor (OFET) device was evaluated and proves to be film thickness dependent. For 40 nm layer thickness it displays a saturation hole mobility (μhole ) of up to 0.01 cm(2)  V(-1)  s(-1) and an on/off-ratio (Ion /Ioff ) of 1.5×10(3) .

  9. Detection of surface mobility of poly (2, 3, 4, 5, 6-pentafluorostyrene) films by in situ variable-temperature ToF-SIMS and contact angle measurements.

    PubMed

    Fu, Yi; Lau, Yiu-Ting R; Weng, Lu-Tao; Ng, Kai-Mo; Chan, Chi-Ming

    2014-10-01

    Poly (2, 3, 4, 5, 6-pentafluorostyrene) (5FPS) was prepared by bulk radical polymerization. The spin-cast films of this polymer were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS) at various temperatures ranging from room temperature to 120°C. Principal component analysis (PCA) of the ToF-SIMS data revealed a transition temperature (T(T)) at which the surface structure of 5FPS was rearranged. A comparison between the results of the PCA of ToF-SIMS spectra obtained on 5FPS and polystyrene (PS) indicate that the pendant groups of 5FPS and PS moved in exactly opposite directions as the temperature increased. More pendant groups of 5FPS and PS migrated from the bulk to the surface and verse versa, respectively, as the temperature increased. These results clearly support the view that the abrupt changes in the normalized principal component 1 value was caused by the surface reorientation of the polymers and not by a change in the ion fragmentation mechanism at temperatures above the T(T). Contact angle measurement, which is another extremely surface sensitive technique, was used to monitor the change in the surface tension as a function of temperature. A clear T(T) was determined by the contact angle measurements. The T(T) values determined by contact angle measurements and ToF-SIMS were very similar.

  10. Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of 2,3,4,5,6-Pentafluoro-trans-cinnamic acid.

    PubMed

    Sert, Yusuf; Doğan, Hatice; Navarrete, Angélica; Somanathan, Ratnasamy; Aguirre, Gerardo; Çırak, Çağrı

    2014-07-15

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized 2,3,4,5,6-Pentafluoro-trans-cinnamic acid have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and DFT/M06-2X (the highly parameterized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted.

  11. Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of 2,3,4,5,6-Pentafluoro-trans-cinnamic acid

    NASA Astrophysics Data System (ADS)

    Sert, Yusuf; Doğan, Hatice; Navarrete, Angélica; Somanathan, Ratnasamy; Aguirre, Gerardo; Çırak, Çağrı

    2014-07-01

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized 2,3,4,5,6-Pentafluoro-trans-cinnamic acid have been investigated. The experimental FT-IR (4000-400 cm-1) and Laser-Raman spectra (4000-100 cm-1) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and DFT/M06-2X (the highly parameterized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted.

  12. Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol using a novel bacterium Ochrobactrum sp. JAS2: A proposal of its metabolic pathway.

    PubMed

    Abraham, Jayanthi; Silambarasan, Sivagnanam

    2016-01-01

    Biodegradation of chlorpyrifos and its major metabolite 3,5,6-trichloro-2-pyridinol (TCP) were studied with a novel bacterial strain JAS2 isolated from paddy rhizosphere soil. The molecular characterization based on 16S rRNA gene sequence homology confirmed its identity as Ochrobactrum sp. JAS2. The JAS2 strain degraded 300mgl(-1) of chlorpyrifos within 12h of incubation in the aqueous medium and it produced the TCP metabolite. However, after 72h of incubation TCP was also completely degraded by the JAS2 strain. A tentative degradation pathway of chlorpyrifos by Ochrobactrum sp. JAS2 has been proposed on basis of GC-MS analysis. The complete degradation of chlorpyrifos occurred within 24h in the soil spiked with and without addition of nutrients inoculated with Ochrobactrum sp. JAS2. TCP was obtained in both the studies which was degraded completely by 96h in the soil spiked with nutrients and whereas 120h in absence of nutrients in the soil. The mpd gene which is responsible for organophosphorus hydrolase production was identified. The isolates Ochrobactrum sp. JAS2 also exhibited a time dependent increase in the amount of tricalcium phosphate solubilization in Pikovskaya's medium. Further screening of the strain JAS2 for auxiliary plant growth promoting activities revealed its remarkable capability of producing the indole acetic acid (IAA), hydrogen cyanide (HCN) and ammonia.

  13. Design, Synthesis, and Pharmacological Evaluation of 5,6-Disubstituted Pyridin-2(1H)-one Derivatives as Phosphodiesterase 10A (PDE10A) Antagonists.

    PubMed

    Lingam, V S Prasadarao; Dahale, Dnyaneshwar H; Rathi, Vijay E; Shingote, Yogesh B; Thakur, Rajni R; Mindhe, Ajit S; Kummari, Srinivas; Khairatkar-Joshi, Neelima; Bajpai, Malini; Shah, Daisy M; Sapalya, Ratika S; Gullapalli, Srinivas; Gupta, Praveen K; Gudi, Girish S; Jadhav, Satyawan B; Pattem, Rambabu; Thomas, Abraham

    2015-10-22

    We report the design and synthesis of novel 5,6-diarylated pyridin-2(1H)-one derivatives as pharmacophoric PDE10A inhibitors. This highly potent molecular scaffold was developed from an inactive diarylpyridine-2-amine derivative 3b by extensive and systematic analogue synthesis and SAR analysis. Further optimization of the scaffold resulted in identification of pyridin-2(1H)-one 18b as a lead compound with good potency (IC50 = 1.6 nM) and selectivity (>6000-fold) over other related PDEs but with a poor pharmacokinetic profile. Careful metabolite profiling of 18b revealed that poor systemic exposure in rats (Cmax = 44 ng/mL; AUC0-t = 359 ng · h/mL) at 10 mg/kg was due to the formation of O-glucuronide conjugate by phase 2 metabolism. The structure of the glucuronide metabolite was confirmed by retention time and LC-MS/MS fragmentation matching with the synthetic glucuronide 26. The problem of low exposure of 18b was effectively addressed by its conversion to an acetate prodrug 25b, which upon oral dosing resulted in an improved pharmacokinetic profile (Cmax = 359 ng.h/mL; AUC0-t = 2436 ng.h/mL) and a desirable brain to plasma ratio of 1.2. The prodrug 25b showed good efficacy in selected rodent models of psychosis.

  14. Technology, Time and Transition in Higher Education--Two Different Realities of Everyday "Facebook" Use in the First Year of University in the UK

    ERIC Educational Resources Information Center

    Stirling, Eve

    2016-01-01

    Within the range of websites and apps that are part of first-year undergraduates' digital environments, the social network site "Facebook" is perhaps the most popular and prominent. As such, the ubiquitous nature of "Facebook" in the higher education landscape has drawn much attention from scholars. Drawing on data from a…

  15. Providing Higher Education in Post-Modern Times: What Do University Mission Statements Tell Us about What They Believe and Do?

    ERIC Educational Resources Information Center

    Ellis, Jennifer; Miller, Paul

    2014-01-01

    Higher education institutions (HEIs) are critical to the delivery of education for all in any nation state. What they believe and what they do are critical components to creating societal impact. But what they believe and do is not always clear. Using a derivative of SWIFT (Structured Word Identification and Frequency Totals), the authors examined…

  16. Assessing the Impact of a Statewide STEM Investment on K-12, Higher Education, and Business/Community STEM Awareness over Time

    ERIC Educational Resources Information Center

    Sondergeld, Toni A.; Johnson, Carla C.; Walten, Janet B.

    2016-01-01

    Despite monetary and educational investments in science, technology, engineering, and mathematics (STEM) being at record high levels, little attention has been devoted to generating a common understanding of STEM. In addition, working with business, K-12 schools, and/or institutions of higher education to establish a grassroots effort to help…

  17. Problem Solving by 5-6 Years Old Kindergarten Children in a Computer Programming Environment: A Case Study

    ERIC Educational Resources Information Center

    Fessakis, G.; Gouli, E.; Mavroudi, E.

    2013-01-01

    Computer programming is considered an important competence for the development of higher-order thinking in addition to algorithmic problem solving skills. Its horizontal integration throughout all educational levels is considered worthwhile and attracts the attention of researchers. Towards this direction, an exploratory case study is presented…

  18. Comprehensive DFT and TD-DFT Studies on the Photophysical Properties of 5,6-Dichloro-1,3-Bis(2-Pyridylimino)-4,7-Dihydroxyisoindole: A New Class of ESIPT Fluorophore.

    PubMed

    Kataria, Santosh; Rhyman, Lydia; Ramasami, Ponnadurai; Sekar, Nagaiyan

    2016-09-01

    Hanson et al. [Org. Lett., 2011] reported the absorption and emission spectrum of 5,6-dichloro-1,3-bis(2-pyridylimino)-4,7-dihydroxyisoindole but the excited-state intramolecular proton transfer (ESIPT) process was not investigated. The photo-physical behaviour of 5,6-dichloro-1,3-bis(2-pyridylimino)-4,7-dihydroxyisoindole was studied using the density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The functional used was B3LYP and 6-31G(d) was the basis set for all the atoms. All the ten tautomers were studied for the absorption and emission properties. It is found that the tautomer where hydroxyl groups are syn to nitrogen of isoindoline ring is most stable and thus, responsible for the ESIPT process. The computed absorption and emission values of tautomers using TD-DFT are in good agreement with those obtained experimentally.

  19. Near-infrared absorbing and emitting Ru(II)-Pt(II) heterodimetallic complexes of dpdpz (dpdpz = 2,3-di(2-pyridyl)-5,6-diphenylpyrazine).

    PubMed

    Wu, Si-Hai; Burkhardt, Stephen E; Yao, Jiannian; Zhong, Yu-Wu; Abruña, Héctor D

    2011-05-02

    The reaction of 2,3-di(2-pyridyl)-5,6-diphenylpyrazine (dpdpz) with K(2)PtCl(4) in a mixture of acetonitrile and water afforded mono-Pt complex (dpdpz)PtCl(2)4 in good yield, with two lateral pyridine nitrogen atoms binding to the metal center. Two types of Ru(II)-Pt(II) heterodimetallic complexes bridged by dpdpz, namely, [(bpy)(2)Ru(dpdpz)Pt(C≡CC(6)H(4)R)](2+) (7-9, R = H, NMe(2), or Cl, respectively) and [(tpy)Ru(dpdpz)Pt(C≡CPh)] (+) (12), were then designed and prepared, where bpy = 2,2'-bipyridine and tpy = 2,2';6',2''-terpyridine. In both cases, the platinum atom binds to dpdpz with a C(∧)N(∧)N tridentate mode. However, the coordination of the ruthenium atom with dpdpz could either be noncyclometalated (N(∧)N bidentate) or cyclometalated (C(∧)N(∧)N tridentate). The electronic properties of these complexes were subsequently studied and compared by spectroscopic and electrochemical analyses and theoretical calculations. These complexes exhibit substantial absorption in the visible to NIR (near-infrared) region because of mixed MLCT (metal-to-ligand-charge-tranfer) transitions from both the ruthenium and the platinum centers. Complexes 7 and 9 were found to emit NIR light with higher quantum yields than those of the mono-Ru complex [(bpy)(2)Ru(dpdpz)](2+) (5) and bis-Ru complex [(bpy)(2)Ru(dpdpz)Ru(bpy)(2)](4+) (13). However, no emission was detected from complex 8 or 12 at room temperature in acetonitrile.

  20. 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.

  1. Dinuclear Ru/Ni, Ir/Ni, and Ir/Pt complexes with bridging phenanthroline-5,6-dithiolate: synthesis, structure, and electrochemical and photophysical behavior.

    PubMed

    Schallenberg, David; Neubauer, Antje; Erdmann, Elisa; Tänzler, Marco; Villinger, Alexander; Lochbrunner, Stefan; Seidel, Wolfram W

    2014-09-02

    We report the synthesis and full characterization of dinuclear complexes with the bridging ligand phenanthroline-5,6-dithiolate (phendt(2-)) featuring the [Ru(bpy)2](2+) or Ir(ppy)2](+) fragment at the diimine donor center and the [Ni(dppe)](2+) or [Pt(phen)](2+) complex moiety at the dithiolate group. The molecular structures of the mononuclear complexes [(C5H5)2Ti(S,S'-phendt)] and [(ppy)2Ir{N,N'-phendt-(C2H4CN)2}](PF6) as well as the dinuclear complex [(C5H5)(PPh3)Ru(phendt)Ni(dppe)](PF6) determined by X-ray diffraction (XRD) studies are compared. Photophysical studies with mononuclear [(bpy)2Ru{phendt-(C2H4CN)2}](2+) and [(ppy)2Ir{phendt-(C2H4CN)2}](+) as well as dinuclear [(bpy)2Ru(phendt)Ni(dppe)](2+) and [(ppy)2Ir(phendt)Ni(dppe)](+) uncovered an effective luminescence quenching in the dinuclear complexes. Lifetime measurements at room temperature, steady-state measurements at low temperature, electrochemical investigations, and DFT calculations provide evidence for a very efficient energy transfer from the Ru/Ir to the Ni complex moiety with a rate constant k > 5 × 10(9) s(-1). In comparison, the [Ru]phendt[Ni] complex displays a higher quenching efficiency with reduced excited state lifetime, whereas the [Ir]phendt[Ni] complex is characterized by an unaltered lifetime of the thermally equilibrated excited state.

  2. Thalidomide increases both intra-tumoural tumour necrosis factor-α production and anti-tumour activity in response to 5,6-dimethylxanthenone-4-acetic acid

    PubMed Central

    Cao, Z; Joseph, W R; Browne, W L; Mountjoy, K G; Palmer, B D; Baguley, B C; Ching, L-M

    1999-01-01

    5,6-Dimethylxanthenone-4-acetic acid (DMXAA), synthesized in this laboratory and currently in phase I clinical trial, is a low molecular weight inducer of tumour necrosis factor-α (TNF-α). Administration of DMXAA to mice with established transplantable tumours elicits rapid vascular collapse selectively in the tumour, followed by extensive haemorrhagic necrosis mediated primarily through the production of TNF-α. In this report we have investigated the synthesis of TNF-α mRNA in hepatic, splenic and tumour tissue. Co-administration of thalidomide with DMXAA increased anti-tumour activity and increased intra-tumoural TNF-α production approximately tenfold over that obtained with DMXAA alone. Thalidomide increased splenic TNF-α production slightly but significantly decreased serum and hepatic levels of TNF-α induced with DMXAA. Lipopolysaccharide (LPS) induced 300-fold higher serum TNF-α than did DMXAA at the maximum tolerated dose, but induced similar amounts of TNF-α in spleen, liver and tumour. Splenic TNF-α activity induced with LPS was slightly increased with thalidomide, but serum and liver TNF-α levels were suppressed. Thalidomide did not increase intra-tumoural TNF-α production induced with LPS, in sharp contrast to that obtained with DMXAA. While thalidomide improved the anti-tumour response to DMXAA, it had no effect on the anti-tumour action of LPS that did not induce a significant growth delay or cures against the Colon 38 tumour. The increase in the anti-tumour action by thalidomide in combination with DMXAA corresponded to an increase in intra-tumoural TNF-α production. Co-administration of thalidomide may represent a novel approach to improving selective intra-tumoural TNF-α production and anti-tumour efficacy of DMXAA. © 1999 Cancer Research Campaign PMID:10360649

  3. Response function of NE213 scintillator for 0.5-6 MeV neutrons measured by an improved pulse shape discrimination

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Lee, C. S.

    1998-02-01

    Using the pulse shape discrimination method combined with the time of flight technique, we have obtained the response function of a 2″ diameter × 2″ thick NE213 scintillator by measuring directly the proton recoil energy spectrum of 0.5-6 MeV prompt neutrons from a 252Cf source. Three parameters, time of flight (TOF), pulse shape discrimination (PSD) and recoil energy (RE), were recorded in an event-by-event mode with a TOF gate. We attempted to improve the determination of maximum proton recoil energies equal to incident neutron energies by employing two analysis methods. First, we attempted to separate better neutrons from coexisting gamma rays in the PSD spectrum by projecting neutron channels of the PSD spectrum onto both TOF and RE spectra in a cubic matrix constructed by the three-parameter data. The resulting two-dimensional matrix composed of TOF and RE channels was free from gamma rays and corresponding Compton-recoiled electrons, and then projected with neutron energy bins of 0.05 MeV wide determined by TOF. Finally, to determine the maximum proton recoil energies from each RE spectrum with a realistic function, accounting for the nonlinear response of the NE213 scintillator due to the quenching effect, we performed a least-squares fit to the RE spectrum using the four-parameter function. The response function obtained in the present work agrees well with previous experimental results obtained by Gul et al. (Nucl. Instr. and Meth. A 278 (1989) 470) and a Monte Carlo study by Cecil et al. (Nucl. Instr. and Meth. 161 (1979) 439).

  4. Effects of 5,6-Dihydroxy-2,4-Dimethoxy-9,10-Dihydrophenanthrene on G2/M Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells.

    PubMed

    Duangprompo, Wipada; Aree, Kalaya; Itharat, Arunporn; Hansakul, Pintusorn

    2016-01-01

    5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (HMP) is an active compound isolated from the rhizome extracts of Dioscorea membranacea Pierre, a Thai medicinal plant. This study aimed to investigate the growth-inhibitory and apoptosis-inducing effects of HMP in human lung cancer A549 cells. The antiproliferative and cytotoxic effects of HMP were analyzed by a Sulforhodamine B assay. Cell division, cell cycle distribution and membrane asymmetry changes were each performed with different fluorescent dyes and then analyzed by flow cytometry. Real-time PCR and immunoblotting were used to detect cell cycle- and apoptosis-related mRNA levels and proteins, respectively. The nuclear morphology of the cells stained with DAPI and DNA fragmentation were detected by fluorescence microscopy and gel electrophoresis, respectively. The results showed that HMP exerted strong antiproliferative and cytotoxic activities in A549 cells with the highest selectivity index. It halted the cell cycle in [Formula: see text]/M phase via down-regulation of the expression levels of regulatory proteins Cdc25C, Cdk1 and cyclinB1. In addition, HMP induced early apoptotic cells with externalized phosphatidylserine and subsequent apoptotic cells in sub-[Formula: see text] phase. HMP increased caspase-3 activity and levels of the cleaved (active) form of caspase-3 whose actions were supported by the cleavage of its target PARP, nuclear condensation and DNA apoptotic ladder. Moreover, HMP significantly increased the mRNA and protein levels of proapoptotic Bax as well as promoted subsequent caspase-9 activation and BID cleavage, indicating HMP-induced apoptosis via both intrinsic and extrinsic pathways. These data support, for the first time, the potential role of HMP as a cell-cycle arrest and apoptosis-inducing agent for lung cancer treatment.

  5. 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

  6. 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.

  7. USSR Report, Military Affairs, No. 1780, Communist of the Armed Forces, Nos. 5-6, March 1983

    DTIC Science & Technology

    1983-07-19

    keeps them in an exemplary state and is able to control them under the most complex situation and to quickly take correct decisions. The results of...possibility of constantly keeping the coastal states in its sights. Secondly, as the Indian newspaper NAV BHARAT TIMES emphasizes, to land an assault force...order to shorten the time for increasing the grouping of its armed forces for operations in the Indian Ocean, the United States is constant- ly keeping

  8. The Use of Quantile Regression to Forecast Higher Than Expected Respiratory Deaths in a Daily Time Series: A Study of New York City Data 1987-2000

    PubMed Central

    Soyiri, Ireneous N.; Reidpath, Daniel D.

    2013-01-01

    Forecasting higher than expected numbers of health events provides potentially valuable insights in its own right, and may contribute to health services management and syndromic surveillance. This study investigates the use of quantile regression to predict higher than expected respiratory deaths. Data taken from 70,830 deaths occurring in New York were used. Temporal, weather and air quality measures were fitted using quantile regression at the 90th-percentile with half the data (in-sample). Four QR models were fitted: an unconditional model predicting the 90th-percentile of deaths (Model 1), a seasonal / temporal (Model 2), a seasonal, temporal plus lags of weather and air quality (Model 3), and a seasonal, temporal model with 7-day moving averages of weather and air quality. Models were cross-validated with the out of sample data. Performance was measured as proportionate reduction in weighted sum of absolute deviations by a conditional, over unconditional models; i.e., the coefficient of determination (R1). The coefficient of determination showed an improvement over the unconditional model between 0.16 and 0.19. The greatest improvement in predictive and forecasting accuracy of daily mortality was associated with the inclusion of seasonal and temporal predictors (Model 2). No gains were made in the predictive models with the addition of weather and air quality predictors (Models 3 and 4). However, forecasting models that included weather and air quality predictors performed slightly better than the seasonal and temporal model alone (i.e., Model 3 > Model 4 > Model 2) This study provided a new approach to predict higher than expected numbers of respiratory related-deaths. The approach, while promising, has limitations and should be treated at this stage as a proof of concept. PMID:24147122

  9. The use of quantile regression to forecast higher than expected respiratory deaths in a daily time series: a study of New York City data 1987-2000.

    PubMed

    Soyiri, Ireneous N; Reidpath, Daniel D

    2013-01-01

    Forecasting higher than expected numbers of health events provides potentially valuable insights in its own right, and may contribute to health services management and syndromic surveillance. This study investigates the use of quantile regression to predict higher than expected respiratory deaths. Data taken from 70,830 deaths occurring in New York were used. Temporal, weather and air quality measures were fitted using quantile regression at the 90th-percentile with half the data (in-sample). Four QR models were fitted: an unconditional model predicting the 90th-percentile of deaths (Model 1), a seasonal/temporal (Model 2), a seasonal, temporal plus lags of weather and air quality (Model 3), and a seasonal, temporal model with 7-day moving averages of weather and air quality. Models were cross-validated with the out of sample data. Performance was measured as proportionate reduction in weighted sum of absolute deviations by a conditional, over unconditional models; i.e., the coefficient of determination (R1). The coefficient of determination showed an improvement over the unconditional model between 0.16 and 0.19. The greatest improvement in predictive and forecasting accuracy of daily mortality was associated with the inclusion of seasonal and temporal predictors (Model 2). No gains were made in the predictive models with the addition of weather and air quality predictors (Models 3 and 4). However, forecasting models that included weather and air quality predictors performed slightly better than the seasonal and temporal model alone (i.e., Model 3 > Model 4 > Model 2) This study provided a new approach to predict higher than expected numbers of respiratory related-deaths. The approach, while promising, has limitations and should be treated at this stage as a proof of concept.

  10. Chromatin association of XRCC5/6 in the absence of DNA damage depends on the XPE gene product DDB2

    PubMed Central

    Fantini, Damiano; Huang, Shuo; Asara, John M.; Bagchi, Srilata; Raychaudhuri, Pradip

    2017-01-01

    Damaged DNA-binding protein 2 (DDB2), a nuclear protein, participates in both nucleotide excision repair and mRNA transcription. The transcriptional regulatory function of DDB2 is significant in colon cancer, as it regulates metastasis. To characterize the mechanism by which DDB2 participates in transcription, we investigated the protein partners in colon cancer cells. Here we show that DDB2 abundantly associates with XRCC5/6, not involving CUL4 and DNA-PKcs. A DNA-damaging agent that induces DNA double-stranded breaks (DSBs) does not affect the interaction between DDB2 and XRCC5. In addition, DSB-induced nuclear enrichment or chromatin association of XRCC5 does not involve DDB2, suggesting that the DDB2/XRCC5/6 complex represents a distinct pool of XRCC5/6 that is not directly involved in DNA break repair (NHEJ). In the absence of DNA damage, on the other hand, chromatin association of XRCC5 requires DDB2. We show that DDB2 recruits XRCC5 onto the promoter of SEMA3A, a DDB2-stimulated gene. Moreover, depletion of XRCC5 inhibits SEMA3A expression without affecting expression of VEGFA, a repression target of DDB2. Together our results show that DDB2 is critical for chromatin association of XRCC5/6 in the absence of DNA damage and provide evidence that XRCC5/6 are functional partners of DDB2 in its transcriptional stimulatory activity. PMID:28035050

  11. Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 alpha-oxide and certain xenobiotic alkene and arene oxides.

    PubMed

    Levin, W; Michaud, D P; Thomas, P E; Jerina, D M

    1983-02-01

    Metabolism of cholesterol 5,6 alpha-oxide to the 5,6-glycol is catalyzed by a rat liver microsomal epoxide hydrolase that is distinct from the microsomal epoxide hydrolase that metabolizes a wide range of xenobiotic alkene and arene oxides. The two enzymes are antigenically distinct, and the purified microsomal epoxide hydrolase that metabolizes xenobiotic oxides does not catalyze the hydration of cholesterol 5,6 alpha-oxide. In vivo treatment of rats with inducers of microsomal epoxide hydrolase does not enhance the activity of cholesterol 5,6 alpha-oxide hydrolase and, in some cases, actually depresses enzyme activity in the resultant microsomal preparations. Octene 1,2-oxide and benz[a]anthracene 5,6-oxide, both good substrates for xenobiotic epoxide hydrolase, are not competitive inhibitors of cholesterol oxide hydration by rat liver microsomes. The above results establish the existence of a liver microsomal epoxide hydrolase that is under different regulatory control and that appears to have a different substrate specificity than the well-characterized microsomal epoxide hydrolase involved in the metabolism of a widely diverse group of alkene and arene oxides.

  12. Combined evaluation of CK5/6, ER, p63, and MUC3 for distinguishing breast intraductal papilloma from ductal carcinoma in situ.

    PubMed

    Furuya, Chiemi; Kawano, Hiroo; Yamanouchi, Tsuyoshi; Oga, Atsunori; Ueda, Junko; Takahashi, Mutsuo

    2012-06-01

    The differentiation of intraductal papilloma (IDP) in the breast from ductal carcinoma in situ (DCIS) is sometimes difficult. Fifty papillary lesions (25 DCIS and 25 IDP) were immunohistochemically examined using a panel of antibodies, including CK5/6, ER, p63, Ki-67, chromogranin A, synaptophysin, neuron specific enolase, CD56, MUC1, MUC3, CD44, p21, p27, and p53. The immunohistochemical staining pattern of each antibody was evaluated using the Allred scoring system. Then, the area under curve (AUC) for each antibody was computed by receiver operating characteristic (ROC) analysis. DCIS typically showed high scores for ER and MUC3 reactivity compared with IDP, and the AUC for ER and MUC3 were 0.941 and 0.908, respectively. In contrast, IDP showed high scores for CK5/6 and p63 reactivity compared with DCIS, and the AUC for CK5/6 and p63 were 1.00 and 0.954, respectively. We devised a 'Differential Index' (DI) using the following formula: [S(ER) + S(MUC3)]/[S(CK5/6) + S(p63) + 1]. The distributions of the DI for IDP and DCIS did not overlap when the cutoff value was placed arbitrarily at DI = 1.0. From these results, it is concluded that a panel of four CK5/6, ER, p63, and MUC3 antibodies provide valuable information for differentiating IDP from DCIS.

  13. Spatial and temporal variation in type 1 diabetes incidence in Western Australia from 1991 to 2010: increased risk at higher latitudes and over time.

    PubMed

    Ball, Stephen J; Haynes, Aveni; Jacoby, Peter; Pereira, Gavin; Miller, Laura J; Bower, Carol; Davis, Elizabeth A

    2014-07-01

    This study analysed spatial and temporal variation in childhood incidence of type 1 diabetes mellitus (T1DM) among Western Australia׳s 36 Health Districts from 1991 to 2010. There was a strong latitudinal gradient of 3.5% (95% CI, 0.2-7.2) increased risk of T1DM per degree south of the Equator, as averaged across the range 15-35° south. This pattern is consistent with the hypothesis of vitamin D deficiency at higher latitudes. In addition there was a 2.4% (95% CI, 1.3-3.6) average increase in T1DM incidence per year. These effects could not be explained by population density, socioeconomic status, remoteness or ethnicity.

  14. 41 CFR 302-5.6 - Under what circumstances will I receive a househunting trip expenses allowance?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Property Management Federal Travel Regulation System RELOCATION ALLOWANCES PERMANENT CHANGE OF STATION (PCS... authorized you to perform a househunting trip in advance of the travel (the agency authorization must specify the mode of transportation and the period of time allowed for the trip); (b) You have signed a...

  15. [MATCHE: Management Approach to Teaching Consumer and Homemaking Education.] Proceedings: MATCHE II Workshop (Fresno, California, April 5-6, 1976.)

    ERIC Educational Resources Information Center

    Burrows, Ann, Ed.

    Workshop proceedings in Fresno, California, concerning the development of the Management Approach to Teaching Consumer and Homemaking Education (MATCHE), a preservice home economics teacher education curriculum design, are presented in this report. Presentations from the workshop include unique and timely competency-based individualized…

  16. p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3β signaling axis in dental follicle cells.

    PubMed

    Sakisaka, Yukihiko; Kanaya, Sousuke; Nakamura, Takashi; Tamura, Masato; Shimauchi, Hidetoshi; Nemoto, Eiji

    2016-09-16

    Wnt3a is a secreted glycoprotein that activates the glycogen synthase kinase-3β (GSK3β)/β-catenin signaling pathway through low-density-lipoprotein receptor-related protein (LRP)5/6 co-receptors. Wnt3a has been implicated in periodontal development and homeostasis, as well as in cementum formation. Recently, we have reported that Wnt3a increases alkaline phosphatase expression through the induction of osterix (Osx) expression in dental follicle cells, a precursor of cementoblasts. However, the molecular mechanism by which Wnt3a induces Osx expression is still unknown. In this study, we show that Wnt3a-induced Osx expression was inhibited in the presence of p38 mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and SB202190) at gene and protein levels, as assessed by real-time PCR and immunocytohistochemistry, respectively. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist binding to LRP5/6 co-receptors, did not influence Wnt3a-mediated p38 MAPK phosphorylation, suggesting that Wnt3a activates p38 MAPK through LRP5/6-independent signaling. On the other hand, pretreatment with p38 MAPK inhibitors had no effects on the phosphorylated status of GSK3β and β-catenin as well as β-catenin nuclear translocation, but inhibited Wnt3a-mediated β-catenin transcriptional activity. These findings suggest that p38 MAPK modulates canonical Wnt signaling at the β-catenin transcriptional level without any crosstalk with the Wnt3a-mediated LRP5/6-GSK3β signaling axis and subsequent β-catenin nuclear translocation. These findings expand our knowledge of the mechanisms controlling periodontal development and regeneration.

  17. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family.

    PubMed Central

    Wolfman, N M; Hattersley, G; Cox, K; Celeste, A J; Nelson, R; Yamaji, N; Dube, J L; DiBlasio-Smith, E; Nove, J; Song, J J; Wozney, J M; Rosen, V

    1997-01-01

    Little is known about the regulatory signals involved in tendon and ligament formation, and this lack of understanding has hindered attempts to develop biologically based therapies for tendon and ligament repair. Here we report that growth and differentiation factors (GDFs) 5, 6, and 7, members of the TGF-beta gene superfamily that are most related to the bone morphogenetic proteins, induce neotendon/ligament formation when implanted at ectopic sites in vivo. Analysis of tissue induced by GDF-5, 6, or 7, containing implants by currently available morphological and molecular criteria used to characterize tendon and ligament, adds further evidence to the idea that these GDFs act as signaling molecules during embryonic tendon/ligament formation. In addition, comparative in situ localizations of the GDF-5, 6, and 7 mRNAs suggest that these molecules are important regulatory components of synovial joint morphogenesis. PMID:9218508

  18. 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.

  19. Comparative Pharmacokinetics of the Organophosphorus Insecticide Chlorpyrifos and its Major Metabolites Diethylphosphate, Diethylthiophosphate and 3,5,6-Trichloro-2-pyridinol in the Rat

    SciTech Connect

    Timchalk, Chuck; Busby, Andrea L; Campbell, James A; Needham, Larry L; Barr, Dana

    2007-07-31

    Abstract Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual’s contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with their kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140 μmol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1-3 h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72 h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, ~50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22 ± 3 μmol) > DETP (14 ± 2 μmol) > DEP (1.4 ± 0.7 μmol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.

  20. Dipyrido[4,3-b;5,6-b]acridine derivatives and their ruthenium(II) complexes

    SciTech Connect

    Hung, Chi-Ying; Wang, Tie-Lin; Jang, Youngchan |

    1996-09-25

    Two of the most common bidentate chelating ligands employed in coordination chemistry are 2,2{prime}-bipyridine (bpy) and 1,10-phenanthroline (phen). The latter may be considered as a 3,3{prime}-etheno-bridged derivative of the former. The steric requirements of both ligands are very similar, and differences in the properties of their metal complexes may be mostly attributed to electronic differences arising from the greater electronegativity of phen. The next higher homologue of bpy is 2,2{prime};6,2{double_prime}-terpyridine (tpy), which behave as a tridentate chelator but enjoys many of the same coordination properties as bpy. The coordination chemistry of the analogous 3,3{prime}-etheno-bridged derivatives of tpy has not yet been explored. This report will present the preparation and properties of these derivatives and their complexation with Ru(II).

  1. The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis.

    PubMed

    Hong, Ye; Sonneville, Remi; Agostinho, Ana; Meier, Bettina; Wang, Bin; Blow, J Julian; Gartner, Anton

    2016-03-01

    Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis.

  2. The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy.

    PubMed

    Tsuprykov, Oleg; Ando, Ryotaro; Reichetzeder, Christoph; von Websky, Karoline; Antonenko, Viktoriia; Sharkovska, Yuliya; Chaykovska, Lyubov; Rahnenführer, Jan; Hasan, Ahmed A; Tammen, Harald; Alter, Markus; Klein, Thomas; Ueda, Seiji; Yamagishi, Sho-Ichi; Okuda, Seiya; Hocher, Berthold

    2016-05-01

    Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66% with linagliptin and 92% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different.

  3. During replication stress, non-SMC element 5 (NSE5) is required for Smc5/6 protein complex functionality at stalled forks.

    PubMed

    Bustard, Denise E; Menolfi, Demis; Jeppsson, Kristian; Ball, Lindsay G; Dewey, Sidney Carter; Shirahige, Katsuhiko; Sjögren, Camilla; Branzei, Dana; Cobb, Jennifer A

    2012-03-30

    The Smc5/6 complex belongs to the SMC (structural maintenance of chromosomes) family, which also includes cohesin and condensin. In Saccharomyces cerevisiae, the Smc5/6 complex contains six essential non-Smc elements, Nse1-6. Very little is known about how these additional elements contribute to complex function except for Nse2/Mms21, which is an E3 small ubiquitin-like modifier (SUMO) ligase important for Smc5 sumoylation. Characterization of two temperature-sensitive mutants, nse5-ts1 and nse5-ts2, demonstrated the importance of Nse5 within the Smc5/6 complex for its stability and functionality at forks during hydroxyurea-induced replication stress. Both NSE5 alleles showed a marked reduction in Smc5 sumoylation to levels lower than those observed with mms21-11, a mutant of Mms21 that is deficient in SUMO ligase activity. However, a phenotypic comparison of nse5-ts1 and nse5-ts2 revealed a separation of importance between Smc5 sumoylation and the function of the Smc5/6 complex during replication. Only cells carrying the nse5-ts1 allele exhibited defects such as dissociation of the replisome from stalled forks, formation of fork-associated homologous recombination intermediates, and hydroxyurea sensitivity that is additive with mms21-11. These defects are attributed to a failure in Smc5/6 localization to forks in nse5-ts1 cells. Overall, these data support the premise that Nse5 is important for vital interactions between components within the Smc5/6 complex, and for its functionality during replication stress.

  4. Synthesis and spectroscopic properties of two classes of 5,6-dihydrothymidine derivatives. Action on the Ehrlich's ascites cells thymidine kinase.

    PubMed Central

    Teoule, R; Fouque, B; Cadet, J

    1975-01-01

    Trans (+) and (-) 6-alkoxy-5-bromo-5,6 dihydrothymidine and trans (+) and (-) 6-alkoyloxy-5-bromo-5,6-dihydrothymidine compounds have been prepared. The synthesis of these substances (alkoxy : methoxy, ethoxy, butyloxy and isoamyloxy and alkoyloxy : acetoxy and bensovloxy) is described. Diastereoisomers of all products have been isolated by thin layer chromatography and their spectroscopic properties (IR, UV, NMR, mass spectrometry) studied. These compounds have been shown to be competitive inhibitors of Ehrlich's ascites cells thymidine kinase with respect ot thymidine. PMID:1169761

  5. The synthesis of 2 14C-labelled 2-(3-alkoxyphenyl)-5,6-dihydro-5-trazolo[5, 1-a] isoquinoline compounds, novel antifertility agents.

    PubMed

    Sartori, G; Consonni, P; Omodei-sale, A

    1981-04-01

    2 new compounds, L-10503, 2-(3-methoxyphenyl)-5,6-dihydro-s-triazolo [5,1-a] isoquinoline and DL-204 IT, 2-(3-ethoxyphenyl)-5,6-dihydro-s-triazolo [5,1-a] isoquinoline have been developed in the Lepetit Research Laboratories in Milan, Italy. These compounds have been tested in monkeys and rats and have been shown to terminate pregnancy after a single intramuscular injection. Pharmocokinetical, metabolic, and placental absorption studies of these compounds required synthesis of 14 C labelled forms for both. This article describes in details the laboratory procedures to obtain synthesis of these compounds.

  6. Supplementing lactating dairy cows with a vitamin B12 precursor, 5,6-dimethylbenzimidazole, increases the apparent ruminal synthesis of vitamin B12.

    PubMed

    Brito, A; Chiquette, J; Stabler, S P; Allen, R H; Girard, C L

    2015-01-01

    Cobalamin (CBL), the biologically active form of vitamin B12, and its analogs, are produced by bacteria only if cobalt supply is adequate. The analogs differ generally by the nucleotide moiety of the molecule. In CBL, 5,6-dimethylbenzimidazole (5,6-DMB) is the base in the nucleotide moiety. The present study aimed to determine if a supplement of 5,6-DMB could increase utilization of dietary cobalt for synthesis of CBL and change ruminal fermentation, nutrient digestibility, omasal flow of nutrients and ruminal protozoa counts. Eight ruminally cannulated multiparous Holstein cows (mean±standard deviation=238±21 days in milk and 736±47 kg of BW) were used in a crossover design. Cows were randomly assigned to a daily supplement of a gelatin capsule containing 1.5 g of 5,6-DMB via the rumen cannula or no supplement. Each period lasted 29 days and consisted of 21 days for treatment adaptation and 8 days for data and samples collection. Five corrinoids, CBL and four cobamides were detected in the total mixed ration and the omasal digesta from both treatments. The dietary supplement of 5,6-DMB increased (P=0.02) apparent ruminal synthesis of CBL from 14.6 to 19.6 (s.e.m. 0.8) mg/day but had no effect (P>0.1) on apparent ruminal synthesis of the four analogs. The supplement of 5,6-DMB had no effect (P>0.1) on milk production and composition, or on protozoal count, ruminal pH and concentrations of volatile fatty acids and ammonia nitrogen in rumen content. The supplement had also no effect (P>0.1) on intake, omasal flow and apparent ruminal digestibility of dry matter, organic matter, NDF, ADF and nitrogenous fractions. Plasma concentration of CBL was not affected by treatments (P=0.98). Providing a preformed part of the CBL molecule, that is, 5,6-DMB, increased by 34% the apparent ruminal synthesis of CBL by ruminal bacteria but had no effect on ruminal fermentation or protozoa count and it was not sufficient to increase plasma concentrations of the vitamin. Even though

  7. Proceedings Hydration and Hyperhydration Issues Concerning Operation Desert Shield Held in San Diego, California on 5-6 November 1990

    DTIC Science & Technology

    1990-11-06

    period of time, as long as that hyperhydratiop doesn’t produce any decrement in performance? Do some of the other operational people have any comments...pure aerobic task where he has musculoskeletal compactivity. He doesn’t have to wear any clothes, and in those situations, it is difficult to predict...heat casualties. Another theory, advanced by Hertzman and Ferguson , is that dehydration results in regulated changes in the temperature regulatory

  8. Numerical approximation of higher-order time-fractional telegraph equation by using a combination of a geometric approach and method of line

    NASA Astrophysics Data System (ADS)

    Hashemi, M. S.; Baleanu, D.

    2016-07-01

    We propose a simple and accurate numerical scheme for solving the time fractional telegraph (TFT) equation within Caputo type fractional derivative. A fictitious coordinate ϑ is imposed onto the problem in order to transform the dependent variable u (x , t) into a new variable with an extra dimension. In the new space with the added fictitious dimension, a combination of method of line and group preserving scheme (GPS) is proposed to find the approximate solutions. This method preserves the geometric structure of the problem. Power and accuracy of this method has been illustrated through some examples of TFT equation.

  9. On the time course of exogenous cueing effects in bilinguals: higher proficiency in a second language is associated with more rapid endogenous disengagement.

    PubMed

    Mishra, Ramesh K; Hilchey, Matthew D; Singh, Niharika; Klein, Raymond M

    2012-01-01

    Previous investigations have demonstrated a bilingual advantage on various aspects of executive control. It remains unclear how the language proficiency of bilinguals might relate to the mechanisms involved in attentional disengagement. In the present investigation, we tested the hypothesis that high bilingual proficiency would lead to a more rapid endogenous disengagement of attention from task-irrelevant peripheral cues. We predicted that more rapid attentional disengagement would result in an earlier appearance of inhibition of return (IOR). In this study Hindi-English bilinguals who differed in their L2 (English) proficiency participated in a target detection task. Visual targets were preceded by uninformative peripheral cues at various stimulus onset asynchronies (SOAs) allowing for us to visualize the time course of cue-related facilitation and inhibition. High-proficient Hindi-English bilinguals showed an earlier appearance of IOR than did low-proficient bilinguals, suggesting increased efficiency in disengagement of attention from task-irrelevant inputs. Furthermore, consistent with the "global" advantage that characterizes bilinguals in many tasks, the high-proficient group outperformed low-proficient bilinguals in overall reaction time.

  10. Benchmarks on automated system and software generation higher flexibility increased productivity and shorter time-to-market by ScaPable software

    NASA Astrophysics Data System (ADS)

    Gerlich, Rainer

    2002-07-01

    "ScaPable" is an acronym derived from "scalable" and "portable". The attribute "scalable" indicates that specific application software can automatically be built from scratch and verified without writing any statement in a programming language like C, thereby covering a large variety of embedded and/or distributed applications. The term "portable" addresses the capability to automatically port parts of such an application from one physical node to another one - the processor and operating system type may change - only requiring the names of the nodes, their processor type and operating system. This way the infrastructure of an embedded / distributed system can be built just by provision of literals and figures which define the system interaction, communication, topology and performance. Moreover, dedicated application software like needed for on-board command handling, data acquisition and processing, and telemetry handling can be built from generic templates. The generation time range from less than one second up to about twenty minutes on a PC/Linux platform (800 MHz). By this extremely short generation time risks can be identified early because the executable application is immediately available for validation. A rough estimation shows that one hour of automated system and software generation is equivalent to about 5 .. 50 man years. Currently, about 50% of a typical space embedded system can be covered by the available automated approach. However, the more it is applied, the more can be covered by automation. A system is constructed by applying a formal transformation to the few information as delivered by the user. This approach is not limited to the space domain, although the first industrial application was a space project. Quite different domains can take advantage of such principles of system construction. This paper explains the approach, compares it with other approaches, and provides figures on productivity, duration of system generation and reliability.

  11. Spin Polarization of Rb and Cs np ^{2}P_{3/2} (n=5, 6) Atoms by Circularly Polarized Photoexcitation of a Transient Diatomic Molecule.

    PubMed

    Mironov, A E; Hewitt, J D; Eden, J G

    2017-03-17

    We report the selective population of Rb or Cs np ^{2}P_{3/2} (n=5, 6; F=4, 5) hyperfine states by the photodissociation of a transient, alkali-rare gas diatomic molecule. Circularly polarized (σ^{-}), amplified spontaneous emission (ASE) on the D_{2} line of Rb or Cs (780.0 and 852.1 nm, respectively) is generated when Rb-Xe or Cs-Xe ground state collision pairs are photoexcited by a σ^{+}-polarized optical field having a wavelength within the D_{2} blue satellite continuum, associated with the B^{2}Σ_{1/2}^{+}←X^{2}Σ_{1/2}^{+} (free←free) transition of the diatomic molecule. The degree of spin polarization of Cs (6p ^{2}P_{3/2}), specifically, is found to be dependent on the interatomic distance (R) at which the excited complex is born, a result attributed to the structure of the B^{2}Σ_{1/2}^{+} state. For Cs-Xe atomic pairs, tuning the wavelength of the optical field from 843 to 848 nm varies the degree of circular polarization of the ASE from 63% to almost unity because of the perturbation, in the 5≤R≤6  Å interval, of the ^{2}Σ_{1/2}^{+} potential by a dσ molecular orbital associated with a higher ^{2}Λ electronic state. Monitoring only the Cs 6p ^{2}P_{3/2} spin polarization reveals a previously unobserved interaction of CsXe (B^{2}Σ_{1/2}^{+}) with the lowest vibrational levels of a ^{2}Λ state derived from Cs (5d)+Xe. By inserting a molecular intermediate into the alkali atom excitation mechanism, these experiments realize electronic spin polarization through populating no more than two np ^{2}P_{3/2} hyperfine states, and demonstrate a sensitive spectroscopic probe of R-dependent state-state interactions and their impact on interatomic potentials.

  12. Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio

    EPA Science Inventory

    Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TC...

  13. CHLORPYRIFOS AND 3,5,6 TRICHLORO-2-PYRIDINOL DISTRIBUTION IN RAT BLOOD AND BRAIN DURING CHRONIC DIETARY AND REPEATED HIGH LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS.

    EPA Science Inventory

    The aim of this study was to determine the concentrations of an organophosphorus pesticide, chlorpyrifos (CPF), and the metabolite 3,5,6 trichloro-2-pyridinol (TCP) in tissues from rats exposed to long-term, low-dose CPF. Adult, Long-Evans male rats received CPF for one year at ...

  14. EXPOSURE OF PRESCHOOL CHILDREN TO CHLORPYRIFOS AND ITS DEGRADATION PRODUCT 3,5,6-TRICHLORO-2-PYRIDINOL IN THEIR EVERYDAY ENVIRONMENTS

    EPA Science Inventory

    As part of the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study, we investigated the exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol (TCP) in their everyday environment...

  15. Analysing Mothers' Self-Efficacy Perception towards Parenting in Relation to Peer Relationships of 5-6 Year-Old Preschool Children

    ERIC Educational Resources Information Center

    Secer, Zarife; Gulay Ogelman, Hulya; Onder, Alev; Berengi, Semra

    2012-01-01

    The purpose of this study was to investigate the effect of self-efficacy perception of mothers' towards parenting on the peer relations of children aged between 5 and 6. The sample group of this study comprised of 200, 5-6 year old children (girls = 96, boys = 104), and their mothers. The Ladd and Profilet Child Behaviour Scale, the Peer…

  16. Determination of atmospheric amines by on-fiber derivatization solid-phase microextraction with 2,3,4,5,6-pentafluorobenzyl chloroformate and 9-fluorenylmethoxycarbonyl chloride.

    PubMed

    Parshintsev, Jevgeni; Rönkkö, Tuukka; Helin, Aku; Hartonen, Kari; Riekkola, Marja-Liisa

    2015-01-09

    Alkylamines play an important role in atmospheric chemistry and are of concern for human health. Determining them from the vapor phase is challenging owing to their high polarity and volatility, water solubility, low concentrations, and poor chromatographic properties. We propose on-fiber derivatization solid-phase microextraction (SPME) to increase sensitivity and selectivity for the determination of alkylamines in air samples. SPME fibers coated in head-space with 2,3,4,5,6-pentafluorobenzyl chloroformate (PFBCF, 10min) or 9-fluorenylmethoxycarbonyl (FMOC) chloride (5min) were exposed to the sample for 5-120min, after which the derivatized alkylamines were thermally desorbed in the GC injection port and analyzed by GC-MS. The specific focus of the research was dimethylamine (DMA) but, as well as secondary amines, both coating agents readily react with primary and tertiary amines and with ammonia at ambient temperatures. The fiber coating procedures, sampling times, and analytical conditions were optimized, and methods were tested with natural samples. PFBCF was more selective and almost an order of magnitude more sensitive than FMOC chloride. Both reagents are applicable, however, depending on the requirements. With scan mode and use of molecular ion for quantification, the limit of quantification for DMA was 0.17μgL(-1) when derivatized with PFBCF and 3.4μgL(-1) when derivatized with FMOC chloride. When selected ion monitoring was used with the most abundant ion, the limit of quantification for DMA was 2.8ngL(-1). Intermediate reproducibility expressed as relative standard deviation was around 30% with PFBCF and less than 20% with FMOC chloride. Fibers coated with PFBCF could be used at least up to 24h when stored at 4°C and for 5 to 7h when stored at room temperature. After sampling/derivatization, storage time before analysis should not exceed 48h at 4°C or 24h at room temperature. At maximum, the PFBCF-coated fiber can be used in 100 coating

  17. Inhibition of the Smc5/6 Complex during Meiosis Perturbs Joint Molecule Formation and Resolution without Significantly Changing Crossover or Non-crossover Levels

    PubMed Central

    Lilienthal, Ingrid; Kanno, Takaharu; Sjögren, Camilla

    2013-01-01

    Meiosis is a specialized cell division used by diploid organisms to form haploid gametes for sexual reproduction. Central to this reductive division is repair of endogenous DNA double-strand breaks (DSBs) induced by the meiosis-specific enzyme Spo11. These DSBs are repaired in a process called homologous recombination using the sister chromatid or the homologous chromosome as a repair template, with the homolog being the preferred substrate during meiosis. Specific products of inter-homolog recombination, called crossovers, are essential for proper homolog segregation at the first meiotic nuclear division in budding yeast and mice. This study identifies an essential role for the conserved Structural Maintenance of Chromosomes (SMC) 5/6 protein complex during meiotic recombination in budding yeast. Meiosis-specific smc5/6 mutants experience a block in DNA segregation without hindering meiotic progression. Establishment and removal of meiotic sister chromatid cohesin are independent of functional Smc6 protein. smc6 mutants also have normal levels of DSB formation and repair. Eliminating DSBs rescues the segregation block in smc5/6 mutants, suggesting that the complex has a function during meiotic recombination. Accordingly, smc6 mutants accumulate high levels of recombination intermediates in the form of joint molecules. Many of these joint molecules are formed between sister chromatids, which is not normally observed in wild-type cells. The normal formation of crossovers in smc6 mutants supports the notion that mainly inter-sister joint molecule resolution is impaired. In addition, return-to-function studies indicate that the Smc5/6 complex performs its most important functions during joint molecule resolution without influencing crossover formation. These results suggest that the Smc5/6 complex aids primarily in the resolution of joint molecules formed outside of canonical inter-homolog pathways. PMID:24244180

  18. Rutin ameliorates renal fibrosis and proteinuria in 5/6-nephrectomized rats by anti-oxidation and inhibiting activation of TGFβ1-smad signaling

    PubMed Central

    Han, Yu; Lu, Jin-Shan; Xu, Yong; Zhang, Lei; Hong, Bao-Fa

    2015-01-01

    Objectives: Rutin, a polyphenolic flavonoid, was reported to have beneficial effect on drug induced nephropathy. The present study aimed to introduce 5/6 nephrectomized rat model to further evaluate its renal protective effect. Methods: Adult Wistar rats were induced to develop chronic renal failure through 5/6 nephrectomy (5/6 Nx). After that, animals were treated orally with saline, rutin at 15 and 45 mg/kg, and losartan (10 mg/kg) daily for 20 weeks; sham-operated animals were also involved as control. After treatment for 8 and 20 weeks, blood and urine samples were collected for biochemical examination; all the kidney remnants were collected for histological examination. The protein levels of TGF-β1, smad2 and phosphorylated-smad2 (p-smad2) in kidney were measured. Immunohistochemistry was used to analyze the expression of TGF-β1, fibronectin and collagen IV in kidney tissues. Results: Results suggested that rutin could reduce the proteinurea, blood urine nitrogen and blood creatinine in 5/6 Nx animals significantly, as well as oxidation stress in the kidney. By histological examination, rutin administration alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P<0.01). Immunohistochemistry also suggested rutin could reduce the expression of TGF-β1, fibronectin and collagen IV in kidney tissues. By western blot, we found the rutin could reduce the TGF-β1, p-smad2 expression in the kidney tissues of rats. Conclusions: This study suggests that the rutin can improve renal function in 5/6 Nx rats effectively. Its effect may be due to its anti-oxidation and inhibiting TGFβ1-Smad signaling. PMID:26191162

  19. Assessment of induced SAR in children exposed to electromagnetic plane waves between 10 MHz and 5.6 GHz.

    PubMed

    Bakker, J F; Paulides, M M; Christ, A; Kuster, N; van Rhoon, G C

    2010-06-07

    To avoid potentially adverse health effects of electromagnetic fields (EMF), the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined EMF reference levels from the basic restrictions on the induced whole-body-averaged specific absorption rate (SAR(wb)) and the peak 10 g spatial-averaged SAR (SAR(10g)). The objective of this study is to assess if the SAR in children remains below the basic restrictions upon exposure at the reference levels. Finite difference time domain (FDTD) modeling was used to calculate the SAR in six children and two adults when exposed to all 12 orthogonal plane wave configurations. A sensitivity study showed an expanded uncertainty of 53% (SAR(wb)) and 58% (SAR(10g)) due to variations in simulation settings and tissue properties. In this study, we found that the basic restriction on the SAR(wb) is occasionally exceeded for children, up to a maximum of 45% in small children. The maximum SAR(10g) values, usually found at body protrusions, remain under the limit for all scenarios studied. Our results are in good agreement with the literature, suggesting that the recommended ICNIRP reference levels may need fine tuning.

  20. Assessment of induced SAR in children exposed to electromagnetic plane waves between 10 MHz and 5.6 GHz

    NASA Astrophysics Data System (ADS)

    Bakker, J. F.; Paulides, M. M.; Christ, A.; Kuster, N.; van Rhoon, G. C.

    2010-06-01

    To avoid potentially adverse health effects of electromagnetic fields (EMF), the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined EMF reference levels from the basic restrictions on the induced whole-body-averaged specific absorption rate (SARwb) and the peak 10 g spatial-averaged SAR (SAR10g). The objective of this study is to assess if the SAR in children remains below the basic restrictions upon exposure at the reference levels. Finite difference time domain (FDTD) modeling was used to calculate the SAR in six children and two adults when exposed to all 12 orthogonal plane wave configurations. A sensitivity study showed an expanded uncertainty of 53% (SARwb) and 58% (SAR10g) due to variations in simulation settings and tissue properties. In this study, we found that the basic restriction on the SARwb is occasionally exceeded for children, up to a maximum of 45% in small children. The maximum SAR10g values, usually found at body protrusions, remain under the limit for all scenarios studied. Our results are in good agreement with the literature, suggesting that the recommended ICNIRP reference levels may need fine tuning.

  1. Internationalization of Chinese Higher Education

    ERIC Educational Resources Information Center

    Chen, Linhan; Huang, Danyan

    2013-01-01

    This paper probes into the development of internationalization of higher education in China from ancient times to modern times, including the emergence of international connections in Chinese higher education and the subsequent development of such connections, the further development of internationalization of Chinese higher education, and the…

  2. Experimental and theoretical investigations of the sulfite-based polyoxometalate cluster redox series: alpha- and beta-[Mo(18)O(54)(SO(3))(2)](4-/5-/6-).

    PubMed

    Baffert, Carole; Boas, John F; Bond, Alan M; Kögerler, Paul; Long, De-Liang; Pilbrow, John R; Cronin, Leroy

    2006-11-15

    The synthesis, isolation and structural characterization of the sulfite polyoxomolybdate clusters alpha-(D(3h))(C(20)H(44)N)(4){alpha-[Mo(18)O(54)(SO(3))(2)]}CH(3)CN and beta-(D(3d))(C(20)H(44)N)(4){beta-[Mo(18)O(54)(SO(3))(2)]}CH(3)CN is presented. Voltammetric studies in acetonitrile (0.1 M Hx(4)NClO(4), Hx(4)N=tetra-n-hexylammonium) reveal the presence of an extensive series of six one-electron reduction processes for both isomers. Under conditions of bulk electrolysis, the initial [Mo(18)O(54)(SO(3))(2)](4-/5-) and [Mo(18)O(54)(SO(3))(2)](5-/6-) processes produce stable [Mo(18)O(54)(SO(3))(2)](5-) and [Mo(18)O(54)(SO(3))(2)](6-) species, respectively, and the same reduced species may be produced by photochemical reduction. Spectroelectrochemical data imply that retention of structural form results upon reduction, so that both alpha and beta isomers are available at each of the 4-, 5-, and 6-redox levels. However, the alpha isomer is the thermodynamically favored species in both the one- and two-electron-reduced states, with beta-->alpha isomerization being detected in both cases on long time scales (days). EPR spectra also imply that increasing localization of the unpaired electron occurs over the alpha- and beta-[Mo(18)O(54)(SO(3))(2)](5-) frameworks as the temperature approaches 2 K where the EPR spectra show orthorhombic symmetry with different g and hyperfine values for the alpha and beta isomers. Theoretical studies support the observation that it is easier to reduce the alpha cluster than the beta form and also provide insight into the driving force for beta-->alpha isomerization in the reduced state. Data are compared with that obtained for the well studied alpha-[Mo(18)O(54)(SO(4))(2))](4-) sulfate cluster.

  3. Molecular structure investigation of organic cocrystals of 1,10-phenanthroline-5,6-dione with aryloxyacetic acid: a combined experimental and theoretical study.

    PubMed

    Suresh Kumar, G S; Muthu Prabhu, A Antony; Bhuvanesh, N; Ronica, X A V; Kumaresan, S

    2014-11-11

    Two organic cocrystals namely, 1,10-phenanthroline-5,6-dione:2-naphthoxyacetic acid [(phendione)(2-naa)] (1) and 1,10-phenanthroline-5,6-dione:2-formylphenoxyacetic acid [(phendione)(2-fpaa)] (2) were synthesized and studied by single crystal XRD, FT-IR, NMR, thermogravimetric, and powder X-ray diffraction analysis. The molecular properties of cocrystals were studied using density functional theory (DFT), basis set B3LYP/6-31G(d,p). Both cocrystals are stabilized through intermolecular hydrogen bonding (OH⋯N). The total electron density and molecular electrostatic potential surfaces of the cocrystals were constructed by NBO analysis using B3LYP/6-31G(d,p) method to display the electrostatic potential (electron+nuclei) distribution. The energy gap between HOMO and LUMO was measured for both cocrystals.

  4. Molecular structure investigation of organic cocrystals of 1,10-phenanthroline-5,6-dione with aryloxyacetic acid: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Suresh Kumar, G. S.; Antony Muthu Prabhu, A.; Bhuvanesh, N.; Ronica, X. A. V.; Kumaresan, S.

    2014-11-01

    Two organic cocrystals namely, 1,10-phenanthroline-5,6-dione:2-naphthoxyacetic acid [(phendione)(2-naa)] (1) and 1,10-phenanthroline-5,6-dione:2-formylphenoxyacetic acid [(phendione)(2-fpaa)] (2) were synthesized and studied by single crystal XRD, FT-IR, NMR, thermogravimetric, and powder X-ray diffraction analysis. The molecular properties of cocrystals were studied using density functional theory (DFT), basis set B3LYP/6-31G(d,p). Both cocrystals are stabilized through intermolecular hydrogen bonding (Osbnd H⋯N). The total electron density and molecular electrostatic potential surfaces of the cocrystals were constructed by NBO analysis using B3LYP/6-31G(d,p) method to display the electrostatic potential (electron + nuclei) distribution. The energy gap between HOMO and LUMO was measured for both cocrystals.

  5. Genetic structure of Plasmodium vivax using the merozoite surface protein 1 icb5-6 fragment reveals new hybrid haplotypes in southern Mexico

    PubMed Central

    2014-01-01

    Background Plasmodium vivax is a protozoan parasite with an extensive worldwide distribution, being highly prevalent in Asia as well as in Mesoamerica and South America. In southern Mexico, P. vivax transmission has been endemic and recent studies suggest that these parasites have unique biological and genetic features. The msp1 gene has shown high rate of nucleotide substitutions, deletions, insertions, and its mosaic structure reveals frequent events of recombination, maybe between highly divergent parasite isolates. Methods The nucleotide sequence variation in the polymorphic icb5-6 fragment of the msp1 gene of Mexican and worldwide isolates was analysed. To understand how genotype diversity arises, disperses and persists in Mexico, the genetic structure and genealogical relationships of local isolates were examined. To identify new sequence hybrids and their evolutionary relationships with other P. vivax isolates circulating worldwide two haplotype networks were constructed questioning that two portions of the icb5-6 have different evolutionary history. Results Twelve new msp1 icb5-6 haplotypes of P. vivax from Mexico were identified. These nucleotide sequences show mosaic structure comprising three partially conserved and two variable subfragments and resulted into five different sequence types. The variable subfragment sV1 has undergone recombination events and resulted in hybrid sequences and the haplotype network allocated the Mexican haplotypes to three lineages, corresponding to the Sal I and Belem types, and other more divergent group. In contrast, the network from icb5-6 fragment but not sV1 revealed that the Mexican haplotypes belong to two separate lineages, none of which are closely related to Sal I or Belem sequences. Conclusions These results suggest that the new hybrid haplotypes from southern Mexico were the result of at least three different recombination events. These rearrangements likely resulted from the recombination between haplotypes of

  6. Conformational changes in inositol 1,3,4,5,6-pentakisphosphate 2-kinase upon substrate binding: role of N-terminal lobe and enantiomeric substrate preference.

    PubMed

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

    2012-08-24

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP(5) 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP(5). Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP(5) 2-K, which shed light on aspects of substrate recognition. However, failure of IP(5) 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP(5) 2-K in its different conformations by crystallography. Thus, the IP(5) 2-K apo-form structure displays an open conformation, whereas the nucleotide-bound form shows a half-closed conformation, in contrast to the inositide-bound form obtained previously in a closed conformation. Both nucleotide and inositide binding produce large conformational changes that can be understood as two rigid domain movements, although local changes were also observed. Changes in intrinsic fluorescence upon nucleotide and inositide binding are in agreement with the crystallographic findings. Our work suggests that the clasp might be involved in enzyme kinetics, with the N-terminal lobe being essential for inositide binding and subsequent conformational changes. We also show how IP(5) 2-K discriminates between inositol 1,3,4,5-tetrakisphosphate and 3,4,5,6-tetrakisphosphate enantiomers and that substrate preference can be manipulated by Arg(130) mutation. Altogether, these results provide a framework for rational design of specific inhibitors with potential applications as biological tools for in vivo studies, which could assist in the identification of novel roles for IP(5) 2-K in mammals.

  7. Modelling of crystal structure of cis-1,2,3,6 and 3,4,5,6-tetrahydrophthalic anhydrides using lattice energy calculations.

    PubMed

    Fredj, A Ben; Day, G M

    2015-08-01

    Lattice energy calculations using a model potential were performed to model the crystal structures of cis-1,2,3,6- and 3,4,5,6-tetrahydrophthalic (THP) anhydrides. The optimized molecular models using the DFT method at the B3LYP/6-31G** level were found consistent with the available experimental evidence and allowed all differences observed in crystal packing between cis-1,2,3,6- and 3,4,5,6-THP anhydrides to be reproduced. Calculations provide evidence for the presence of dipole-dipole C=O⋯C=O intermolecular interactions and support the idea that the molecules distort from their ideal geometries, improving packing in both crystals. The search for minima in the lattice energy of both crystals amongst the more common space groups with Z' = 1, using a simulated annealing crystal structure prediction procedure followed by lattice energy minimization showed that the observed structure of 3,4,5,6-THP anhydride (Z' = 2) is the thermodynamically most stable, and allowed us to justify why 3,4,5,6-THP anhydride crystallizes in such a complex structure with 16 molecules in the unit cell. The computational model was successful in predicting the second observed form at 173 K for cis-1,2,3,6-THP anhydride as a polymorph, and could predict several hypothetical structures with Z' = 1 that appear competitive with the observed structures. The results of phonon estimates of zero point intermolecular vibrational energy and entropy suggest that crystal structures of cis-1,2,3,6-THP anhydride cannot be predicted solely on the basis of lattice energy; factors other than thermodynamics favor the observed structures.

  8. Vulgarisin A, a new diterpenoid with a rare 5/6/4/5 ring skeleton from the Chinese medicinal plant Prunella vulgaris.

    PubMed

    Lou, Huayong; Zheng, Shan; Li, Tianlei; Zhang, Jianxin; Fei, Yue; Hao, Xiaojiang; Liang, Guangyi; Pan, Weidong

    2014-05-16

    Vulgarisin A (1), a new diterpenoid with an unprecedented 5/6/4/5 fused tetracyclic ring skeleton, has been isolated from the medicinal plant Prunella vulgaris Linn. Its structure was characterized by extensive spectroscopic methods, and the absolute configuration was secured by single crystal X-ray diffraction analysis. Compound 1 showed weak cytotoxicity against human lung carcinoma A549 cells with an IC50 value of 57.0 μM.

  9. A novel one-pot pseudo-five-component synthesis of 4,5,6,7-tetrahydro-1H-1,4-diazepine-5-carboxamide derivatives.

    PubMed

    Shaabani, Ahmad; Maleki, Ali; Mofakham, Hamid; Moghimi-Rad, Jafar

    2008-05-16

    A novel one-pot pseudo-five-component synthesis of 4,5,6,7-tetrahydro-1 H-1,4-diazepine-5-carboxamide derivatives starting from simple and readily available inputs including 2,3-diaminomaleonitrile, a cyclic or acyclic ketone, an isocyanide, and water in the presence of a catalytic amount of p-toluenesulfonic acid in aqueous medium at ambient temperature in high yields is described.

  10. The ratio of cholesterol 5,6-secosterols formed from ozone and singlet oxygen offers insight into the oxidation of cholesterol in vivo

    PubMed Central

    Wentworth, Anita D.; Song, Byeong-Doo; Nieva, Jorge; Shafton, Asher; Tripurenani, Sangeetha; Wentworth, Paul

    2010-01-01

    Ongoing efforts to unravel the origins of the cholesterol 5,6-secosterols (1a and 1b) in biological systems have revealed that the two known chemical routes to these oxysterols; ozonolysis of cholesterol (3) and Hock-cleavage of 5-α-hydroperoxycholesterol (4a), are distinguishable based upon the ratio of the hydrazone derivatives (2a–b) formed in each case and this ratio offers an insight into the chemical origin of the secosterols in vivo. PMID:19462099

  11. The Evans Aldol-Prins cyclization: a general and stereoselective method for the synthesis of 2,3,4,5,6-pentasubstituted tetrahydropyrans.

    PubMed

    Álvarez-Méndez, Sergio J; García, Celina; Martín, Víctor S

    2016-02-25

    A general and stereoselective method to synthesize 2,3,4,5,6-pentasubstituted tetrahydropyrans in three steps starting from three different aldehydes is described. Key substrates β,γ-unsaturated N-acyloxazolidin-2-ones were subjected to an "Evans Aldol-Prins" protocol to generate five σ-bonds and five stereocenters in only a one-pot process with yields up to 60% and excellent stereoselectivities.

  12. Induction of cytochrome P450IA1 in rat colon and liver by indole-3-carbinol and 5,6-benzoflavone.

    PubMed

    Vang, O; Jensen, M B; Autrup, H

    1990-08-01

    It is known that consumption of cruciferous vegetables protects against the chemical induction of cancer in many organs. It has been suggested that this protection is mediated through an effect on the cytochrome P450 monooxygenase system. This system is responsible for the activation of a number of chemical carcinogens to their ultimate forms. In the present study, the effect of indole-3-carbinol (I3C) and 5,6-benzoflavone (5,6BF) on the expression of cytochrome P450IA1 in rat colon and liver has been investigated. Cytochrome P450IA1 mRNA was induced in colon following a single oral administration of I3C or 5,6BF. A biphasic induction profile was obtained with maxima at 4 and 16 h post-administration. Both inducers caused an approximately 2-fold increase in P450IA1 mRNA at 4 h and a 10-fold increase at 16 h. In contrast, both cytochrome P450IA1 and IA2 mRNAs was increased over the control between 4 and 24 h. The total amount of P450IA mRNAs in liver at 4 and 16 h was increased about 2- and 4-fold respectively by I3C; 5,6BF induced the P450IA mRNAs 4- and 5-fold respectively. The expression of cytochrome P450IA1 and IA2 is induced by I3C and several flavones present in cruciferous vegetables. This suggests that one of the protective effects of cruciferous vegetables in the reduction of chemically induced cancer may be regulation of cytochrome P450s involved in the metabolism of the chemical carcinogens.

  13. Women in Higher Education.

    ERIC Educational Resources Information Center

    Pifer, Alan

    Women have traditionally been discriminated against in higher education in both the attainment of degrees and in employment after earning degrees. It has been felt that women are not as capable, reliable, or effective as men in administrative and classroom situations. Statistics show that even at the present time women are underemployed and…

  14. Crystallization and preliminary X-ray diffraction analysis of inositol 1,3,4,5,6-pentakisphosphate kinase from Arabidopsis thaliana

    PubMed Central

    Baños-Sanz, Jose Ignacio; Villate, Maider; Sanz-Aparicio, Julia; Brearley, Charles Alistair; González, Beatriz

    2010-01-01

    Inositol 1,3,4,5,6-pentakisphosphate kinase (IP5 2-K) is an enzyme involved in inositol metabolism that synthesizes IP6 (inositol 1,2,3,4,5,6-hexakisphosphate) from inositol 1,3,4,5,6-pentakisphosphate (IP5) and ATP. IP6 is the major phosphorus reserve in plants, while in mammals it is involved in multiple cellular events such as DNA editing and chromatin remodelling. In addition, IP6 is the precursor of other highly phosphorylated inositols which also play highly relevant roles. IP5 2-K is the only enzyme that phosphorylates the 2-OH axial position of the inositide and understanding its molecular mechanism of substrate specificity is of great interest in cell biology. IP5 2-K from Arabidopsis thaliana has been expressed in Escherichia coli as two different fusion proteins and purified. Both protein preparations yielded crystals of different quality, always in the presence of IP6. The best crystals obtained for X-ray crystallographic analysis belonged to space group P212121, with unit-cell parameters a = 58.124, b = 113.591, c = 142.478 Å. Several diffraction data sets were collected for the native enzyme and two heavy-atom derivatives using a synchrotron source. PMID:20057083

  15. PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism.

    PubMed

    Dikeakos, Jimmy D; Mercure, Chantal; Lacombe, Marie-Josée; Seidah, Nabil G; Reudelhuber, Timothy L

    2007-08-01

    There are seven members of the proprotein convertase (PC) family of secreted serine proteases that cleave their substrates at basic amino acids, thereby activating a variety of hormones, growth factors, and viruses. PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where they carry out the processing of proteins that are secreted from the cell in a regulated manner. Previous studies have identified alpha-helices in the C-termini of the PC1/3 and PC2 proteases that are required for this subcellular targeting. In the current study, we demonstrate that a predicted alpha-helix in the C-terminus of PC5/6A is also critical for the ability of this domain to target a heterologous protein to the regulated secretory pathway of mouse endocrine AtT-20 cells. Analysis of the subcellular distribution of fusion proteins containing the C-terminal domains of PC1/3, PC2 and PC5/6A confirmed that all three domains have the capacity to redirect a constitutively secreted protein to the granule-containing cytoplasmic extensions. Analysis of the predicted structures formed by these three granule-sorting helices shows a correlation between their granule-sorting efficiency and the clustering of hydrophobic amino acids in their granule-targeting helices.

  16. Comparison of clinical outcomes following vitrified warmed day 5/6 blastocyst transfers using solid surface methodology with fresh blastocyst transfers

    PubMed Central

    Muthukumar, K; Kamath, Mohan S; Mangalaraj, Ann M; Aleyamma, TK; Chandy, Achamma; George, Korula

    2013-01-01

    OBJECTIVES: The literature regarding clinical outcomes following day 5/6 vitrified warmed blastocysts transfer has been conflicting. We decided to evaluate and compare the clinical outcomes following vitrified warmed day 5/6 blastocyst transfer using a solid surface vitrification protocol with fresh blastocyst transfers. SETTINGS: University teaching hospital. STUDY DESIGN: A total of 249 women were retrospectively analyzed: 146 fresh day 5 blastocyst (group 1), 57 day 5 vitrified warmed blastocyst (group 2), and 46 vitrified warmed day 6 blastocyst (group 3) transfer cycles. Vitrification was done using solid surface methodology (non immersion protocol). The main outcomes were implantation rates, clinical pregnancy, and live birth rate per embryo transfer. RESULTS: The baseline clinical characteristics were similar among all three groups. The implantation and clinical pregnancy rates following vitrified warmed day 6 blastocyst transfers (20.9% and 32.6%) were significantly lower as compared to day 5 fresh and vitrified warmed day 5 blastocyst transfers (40.3% and 56.1%, 36.3%, and 52.6%). However, there was no significant difference in the live birth rates across the three groups (group 1: 37.6%, group 2: 40.3%, and group 3: 28.2%). CONCLUSION: No statistically significant difference was observed in live birth rates between fresh day 5 blastocyst transfers and vitrified warmed day 5/6 blastocyst transfers. Vitrification of blastocysts using solid surface methodology is an efficient method of cryopreservation. PMID:23869154

  17. 1,2,5,6-Diepoxyhexane and 1,2,7,8-diepoxyoctane cross-link duplex DNA at 5'-GNC sequences.

    PubMed

    Yunes, M J; Charnecki, S E; Marden, J J; Millard, J T

    1996-09-01

    The carcinogenicity of epoxide compounds has been attributed to covalent binding to DNA. Whereas monoepoxides form only monoadducts, diepoxides can form both monoadducts and interstrand cross-links. The latter are believed to be the more significant cytotoxic lesions as diepoxides are frequently more carcinogenic and mutagenic than their monoepoxide analogues. We therefore examined the relative DNA interstrand cross-linking capabilities of several diepoxides with respect to chain length, molecular flexibility, reported carcinogenic potential, and DNA sequences targeted. Using denaturing polyacrylamide gel electrophoresis, we found that 1,2,5,6-diepoxyhexane and 1,2,7,8-diepoxyoctane share the 5'-GNC target sequence previously found for 1,2,3,4-diepoxybutane [Millard, J.T., and White, M.M. (1993) Biochemistry 32, 2120-2124] and that the efficiency of cross-linking this sequence may reflect carcinogenicity, 1,2,5,6-Diepoxycyclooctane, the biologically inactive rigid analogue of 1,2,5,6-diepoxyhexane, was found to be a poor cross-linker of all DNA sequences examined. Moreover, increasing the diepoxyalkane chain length did not result in enhanced cross-linking ability.

  18. Why Does 2,3,5,6-Tetrachlorophenol Generate the Strongest Intrinsic Chemiluminescence among All Nineteen Chlorophenolic Persistent Organic Pollutants during Environmentally-friendly Advanced Oxidation Process?

    NASA Astrophysics Data System (ADS)

    Gao, Hui-Ying; Mao, Li; Shao, Bo; Huang, Chun-Hua; Zhu, Ben-Zhan

    2016-10-01

    We found recently that intrinsic chemiluminescence (CL) could be produced by all 19 chlorophenolic persistent organic pollutants during environmentally-friendly advanced oxidation processes. Interestingly and unexpectedly, the strongest CL was produced not by the most-highly chlorinated pentachlorophenol (PCP), but rather by the less chlorinated 2,3,5,6-tetrachlorophenol (2,3,5,6-TeCP), one of the three tetrachlorophenol (TeCPs) isomers. However, it remains unclear what is the underlying molecular mechanism. Here we show that not only chlorinated quinoid intermediates, but more interestingly, semiquinone radicals were produced during the degradation of the three TeCPs and PCP by Fenton reagents, and the type and yield of which were found to be well correlated with CL generation. We propose that hydroxyl radical-dependent formation of more tetrachlorinated quinoids, quinone-dioxetanes and electronically excited carbonyl species might be responsible for the exceptionally strong CL production by 2,3,5,6-TeCP as compared to PCP and its two isomers. This is the first report showing the critical role of quinoid intermediates and semiquinone radicals in CL generation from polychlorinated phenols and Fenton system. These new findings may have broad chemical and environmental implications for future studies on remediation of other halogenated persistent aromatic pollutants by advanced oxidation processes.

  19. Why Does 2,3,5,6-Tetrachlorophenol Generate the Strongest Intrinsic Chemiluminescence among All Nineteen Chlorophenolic Persistent Organic Pollutants during Environmentally-friendly Advanced Oxidation Process?

    PubMed Central

    Gao, Hui-Ying; Mao, Li; Shao, Bo; Huang, Chun-Hua; Zhu, Ben-Zhan

    2016-01-01

    We found recently that intrinsic chemiluminescence (CL) could be produced by all 19 chlorophenolic persistent organic pollutants during environmentally-friendly advanced oxidation processes. Interestingly and unexpectedly, the strongest CL was produced not by the most-highly chlorinated pentachlorophenol (PCP), but rather by the less chlorinated 2,3,5,6-tetrachlorophenol (2,3,5,6-TeCP), one of the three tetrachlorophenol (TeCPs) isomers. However, it remains unclear what is the underlying molecular mechanism. Here we show that not only chlorinated quinoid intermediates, but more interestingly, semiquinone radicals were produced during the degradation of the three TeCPs and PCP by Fenton reagents, and the type and yield of which were found to be well correlated with CL generation. We propose that hydroxyl radical-dependent formation of more tetrachlorinated quinoids, quinone-dioxetanes and electronically excited carbonyl species might be responsible for the exceptionally strong CL production by 2,3,5,6-TeCP as compared to PCP and its two isomers. This is the first report showing the critical role of quinoid intermediates and semiquinone radicals in CL generation from polychlorinated phenols and Fenton system. These new findings may have broad chemical and environmental implications for future studies on remediation of other halogenated persistent aromatic pollutants by advanced oxidation processes. PMID:27748358

  20. The Pan-STARRS1 Distant z > 5.6 Quasar Survey: More than 100 Quasars within the First Gyr of the Universe

    NASA Astrophysics Data System (ADS)

    Bañados, E.; Venemans, B. P.; Decarli, R.; Farina, E. P.; Mazzucchelli, C.; Walter, F.; Fan, X.; Stern, D.; Schlafly, E.; Chambers, K. C.; Rix, H.-W.; Jiang, L.; McGreer, I.; Simcoe, R.; Wang, F.; Yang, J.; Morganson, E.; De Rosa, G.; Greiner, J.; Baloković, M.; Burgett, W. S.; Cooper, T.; Draper, P. W.; Flewelling, H.; Hodapp, K. W.; Jun, H. D.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Metcalfe, N.; Miller, D.; Schindler, J.-T.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Yang, Q.

    2016-11-01

    Luminous quasars at z\\gt 5.6 can be studied in detail with the current generation of telescopes and provide us with unique information on the first gigayear of the universe. Thus far, these studies have been statistically limited by the number of quasars known at these redshifts. Such quasars are rare, and therefore, wide-field surveys are required to identify them, and multiwavelength data are required to separate them efficiently from their main contaminants, the far more numerous cool dwarfs. In this paper, we update and extend the selection for the z˜ 6 quasars presented in Bañados et al. (2014) using the Pan-STARRS1 (PS1) survey. We present the PS1 distant quasar sample, which currently consists of 124 quasars in the redshift range 5.6≲ z≲ 6.7 that satisfy our selection criteria. Of these quasars, 77 have been discovered with PS1, and 63 of them are newly identified in this paper. We present the composite spectra of the PS1 distant quasar sample. This sample spans a factor of ˜20 in luminosity and shows a variety of emission line properties. The number of quasars at z\\gt 5.6 presented in this work almost doubles the previously known quasars at these redshifts, marking a transition phase from studies of individual sources to statistical studies of the high-redshift quasar population, which was impossible with earlier, smaller samples.

  1. Teaching Music, Grades 5, 6.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

    This curriculum guide has been prepared for use by both the music specialist and the classroom teacher in New York City. It outlines areas of musical subject matter appropriate for students in grades five and six. The materials are presented in six sections. "Rhythmic Experiences" introduces students to a variety of meters and rhythms…

  2. Fluorescence measurement of diode (805 nm) laser-induced release of 5,6-CF from DSPC liposomes for monitoring of temperature: an in vivo study in rat liver using indocyanine green potentiation

    NASA Astrophysics Data System (ADS)

    Mordon, Serge R.; Desmettre, Thomas; Devoisselle, Jean-Marie; Soulie-Begu, Sylvie

    1995-05-01

    This in-vivo study examines the validity of fluorescence measurement of laser-induced release of temperature sensitive liposome-encapsulated dye for monitoring of temperature and prediction of tissue thermal damage. It is performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye and i.v. injection of Indocyanine Green (ICG) for diode laser potentiation. Temperature sensitive liposomes (DSPC: Di- Stearoyl-Phosphatidyl-Choline) are loaded with 5,6-Carboxyfluorescein (5,6-CF). These liposomes (1.5 ml solution) and ICG (1.5 ml solution-5 mg/kg) are injected to adult male wistar rats. Two hours later, the liver is exposed and irradiated with a 0.8 W diode laser using pulses lasting from 1 s to 6 s (fluence ranging from 16 to 98 J/cm+2)). Simultaneously, the fluorescence emission is measured with a fluorescent imaging system. Results show that the fluorescence intensity increases linearly form 18 J/cm2 up to 75 J/cm2. These fluences correspond to surface temperatures between 42°C to 64°C. The measurements appear to be highly reproducible. In this temperature range, the accuracy is +/- 3°C. The maximum intensity is observed immediately after the laser is switched off and a decrease of the fluorescence intensity is observed (27% in 20 minutes) due to the 5.6-CF clearance. However, the ratio (IF/Ibck) remains almost stable over this period of time and the determination of the temperature is still possible with a good accuracy even 20 minutes after laser irradiation. In conclusion, temperature monitoring by using fluorescence measurement of laser-induced release of liposome-encapsulated dye is clearly demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues.

  3. New approach to immunochemical determinations for triclopyr and 3,5,6-trichloro-2-pyridinol by using a bifunctional hapten, and evaluation of polyclonal antiserum.

    PubMed

    Watanabe, Eiki; Hoshino, Ryoko; Kanzaki, Yukiko; Tokumoto, Hiroshi; Kubo, Hiroaki; Nakazawa, Hiroyuki

    2002-06-19

    The present work describes the design and synthesis of the structurally unique hapten, "bifunctional hapten", to produce a group-specific polyclonal antiserum to triclopyr and 3,5,6-trichloro-2-pyridinol. A bifunctional hapten was designed and synthesized by conjugating commercially available Nepsilon-2,4-dinitrophenyl (DNP)-L-lysine to triclopyr, and then coupling this to carrier proteins such as bovine serum albumin (BSA). The synthesized bifunctional hapten greatly raised the antiserum titer in comparison with that of the conventional hapten, triclopyr. Antiserum with a sufficiently high titer to provide the determinations of targeted compounds was obtained only 63 days after the primary immunization. The obtained antiserum showed the highest affinity to triclopyr (IC(50) = 3.5 nM) and 3,5,6-trichloro-2-pyridinol (IC(50) = 5.1 nM) in homologous ELISA. The cross-reactivities to various agrochemicals and some chlorinated phenolic compounds were determined. Significant cross-reactivity was found to the herbicide 2,4,5-T. The antiserum reacted to both triclopyr and its metabolite. Assay sensitivity was evaluated for effects of various assay conditions, including pH value and concentrations of organic solvents and detergents. Under optimized assay conditions, the quantitative working range of triclopyr ELISA was from 0.1 to 5.2 ng/mL with a limit of detection (LOD) of 0.037 ng/mL, and an IC(50) of 0.72 ng/mL. On the other hand, the quantitative working range of 3,5,6-trichloro-2-pyridinol ELISA was from 0.13 to 6.0 ng/mL with a LOD of 0.052 ng/mL, and an IC(50) of 0.95 ng/mL. Water samples fortified with triclopyr or its metabolite at 1, 5, and 10 ng/mL were directly analyzed without extraction and cleanup by the proposed ELISA. The mean recovery was 101.6%, and the mean coefficient of variation (CV) was 7.1% in the case of the triclopyr ELISA. In the case of the 3,5,6-trichloro-2-pyridinol ELISA, the mean recovery was 99.8%, and the mean CV was 9.5%. The proposed

  4. Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

    PubMed Central

    Zonia, Laura; Cordeiro, Sofia; Tupý, Jaroslav; Feijó, José A.

    2002-01-01

    Oscillatory growth of pollen tubes has been correlated with oscillatory influxes of the cations Ca2+, H+, and K+. Using an ion-specific vibrating probe, a new circuit was identified that involves oscillatory efflux of the anion Cl− at the apex and steady influx along the tube starting at 12 μm distal to the tip. This spatial coupling of influx and efflux sites predicts that a vectorial flux of Cl− ion traverses the apical region. The Cl− channel blockers 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)benzoic acid completely inhibited tobacco pollen tube growth at 80 and 20 μM, respectively. Cl− channel blockers also induced increases in apical cell volume. The apical 50 μm of untreated pollen tubes had a mean cell volume of 3905 ± 75 μm3. DIDS at 80 μM caused a rapid and lethal cell volume increase to 6206 ± 171 μm3, which is at the point of cell bursting at the apex. DIDS was further demonstrated to disrupt Cl− efflux from the apex, indicating that Cl− flux correlates with pollen tube growth and cell volume status. The signal encoded by inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4] antagonized pollen tube growth, induced cell volume increases, and disrupted Cl− efflux. Ins(3,4,5,6)P4 decreased the mean growth rate by 85%, increased the cell volume to 5997 ± 148 μm3, and disrupted normal Cl− efflux oscillations. These effects were specific for Ins(3,4,5,6)P4 and were not mimicked by either Ins(1,3,4,5)P4 or Ins(1,3,4,5,6)P5. Growth correlation analysis demonstrated that cycles of Cl− efflux were coupled to and temporally in phase with cycles of growth. A role for Cl− flux in the dynamic cellular events during growth is assessed. Differential interference contrast microscopy and kymographic analysis of individual growth cycles revealed that vesicles can advance transiently to within 2 to 4 μm of the apex during the phase of maximally increasing Cl− efflux, which temporally

  5. Statistical Methods for Protecting Personally Identifiable Information in the Disclosure of Graduation Rates of First-Time, Full-Time Degree- or Certificate-Seeking Undergraduate Students by 2-Year Degree-Granting Institutions of Higher Education. Technical Brief. NCES 2012-151

    ERIC Educational Resources Information Center

    Chen, Xianglei; Bersudskaya, Vera; Cubarrubi, Archie

    2011-01-01

    The Higher Education Opportunity Act of 2008 (HEOA) requires that Title IV degree-granting institutions disclose annually the graduation rates of first-time, full-time degree- or certificate-seeking undergraduate students, disaggregated by gender, each major racial/ethnic subgroup, and receipt or non-receipt of a federal Pell grant or subsidized…

  6. Hydrido copper clusters supported by dithiocarbamates: oxidative hydride removal and neutron diffraction analysis of [Cu7(H){S2C(aza-15-crown-5)}6].

    PubMed

    Liao, Ping-Kuei; Fang, Ching-Shiang; Edwards, Alison J; Kahlal, Samia; Saillard, Jean-Yves; Liu, C W

    2012-06-18

    Reactions of Cu(I) salts with Na(S(2)CR) (R = N(n)Pr(2), NEt(2), aza-15-crown-5), and (Bu(4)N)(BH(4)) in an 8:6:1 ratio in CH(3)CN solution at room temperature yield the monocationic hydride-centered octanuclear Cu(I) clusters, [Cu(8)(H){S(2)CR}(6)](PF(6)) (R = N(n)Pr(2), 1(H); NEt(2), 2(H); aza-15-crown-5, 3(H)). Further reactions of [Cu(8)(H){S(2)CR}(6)](PF(6)) with 1 equiv of (Bu(4)N)(BH(4)) produced neutral heptanuclear copper clusters, [Cu(7)(H){S(2)CR}(6)] (R = N(n)Pr(2), 4(H); NEt(2), 5(H); aza-15-crown-5, 6(H)) and clusters 4-6 can also be generated from the reaction of Cu(BF(4))(2), Na(S(2)CR), and (Bu(4)N)(BH(4)) in a 7:6:8 molar ratio in CH(3)CN. Reformation of cationic Cu(I)(8) clusters by adding 1 equiv of Cu(I) salt to the neutral Cu(7) clusters in solution is observed. Intriguingly, the central hydride in [Cu(8)(H){S(2)CN(n)Pr(2)}(6)](PF(6)) can be oxidatively removed as H(2) by Ce(NO(3))(6)(2-) to yield [Cu(II)(S(2)CN(n)Pr(2))(2)] exploiting the redox-tolerant nature of dithiocarbamates. Regeneration of hydride-centered octanuclear copper clusters from the [Cu(II)(S(2)CN(n)Pr(2))(2)] can be achieved by reaction with Cu(I) ions and borohydride. The hydride release and regeneration of Cu(I)(8) was monitored by UV-visible titration experiments. To our knowledge, this is the first time that hydride encapsulated within a copper cluster can be released as H(2) via chemical means. All complexes have been fully characterized by (1)H NMR, FT-IR, UV-vis, and elemental analysis, and molecular structures of 1(H), 2(H), and 6(H) were clearly established by single-crystal X-ray diffraction. Both 1(H) and 2(H) exhibit a tetracapped tetrahedral Cu(8) skeleton, which is inscribed within a S(12) icosahedron constituted by six dialkyl dithiocarbamate ligands in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. The copper framework of 6(H) is a tricapped distorted tetrahedron in which the four-coordinate hydride is demonstrated to occupy the central site by

  7. Hepatocyte growth factor counteracts transforming growth factor-beta1, through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice.

    PubMed

    Inoue, Tsutomu; Okada, Hirokazu; Kobayashi, Tatsuya; Watanabe, Yusuke; Kanno, Yoshihiko; Kopp, Jeffrey B; Nishida, Takashi; Takigawa, Masaharu; Ueno, Munehisa; Nakamura, Toshikazu; Suzuki, Hiromichi

    2003-02-01

    We investigated the mechanism of the anti-fibrotic effects of hepatocyte growth factor (HGF) in the kidney, with respect to its effect on connective tissue growth factor (CTGF), a down-stream, profibrotic mediator of transforming growth factor-beta1 (TGF-beta1). In wild-type (WT) mice with 5/6 nephrectomy (Nx), HGF and TGF-beta1 mRNAs increased transiently in the remnant kidney by week 1 after the Nx, returned to baseline levels, and increased again at weeks 4 to 12. In contrast, CTGF and alpha1(I) procollagen (COLI) mRNAs increased in parallel with HGF and TGF-beta1 during the early stage, but did not re-increase during the late stage. In the case of TGF-beta1 transgenic (TG) mice with 5/6 Nx, excess TGF-beta1 derived from the transgene enhanced CTGF expression significantly in the remnant kidney, accordingly accelerating renal fibrogenesis. Administration of dHGF (5.0 mg/kg/day) to TG mice with 5/6 Nx for 4 weeks from weeks 2 to 6 suppressed CTGF expression in the remnant kidney, attenuating renal fibrosis and improving the survival rate. In an experiment in vitro, renal tubulointerstitial fibroblasts (TFB) were co-cultured with proximal tubular epithelial cells (PTEC). Pretreatment with HGF reduced significantly CTGF induction in PTEC by TGF-beta1, consequently suppressing COLI synthesis in TFB. In conclusion, HGF can block, at least partially, renal fibrogenesis promoted by TGF-beta1 in the remnant kidney, via attenuation of CTGF induction.

  8. Transcriptional profiling of canola developing embryo and identification of the important roles of BnDof5.6 in embryo development and fatty acids synthesis.

    PubMed

    Deng, Wei; Yan, Fang; Zhang, Xiaolan; Tang, Yuwei; Yuan, Yujin

    2015-08-01

    Canola is an important vegetable oil crop globally, and the understanding of the molecular mechanism underlying fatty acids biosynthesis during seed embryo development is an important research goal. Here we report the transcriptional profiling analysis of developing canola embryos using RNA-sequencing (RNA-Seq) method. RNA-Seq analysis generated 58,579,451 sequence reads aligned with 32,243 genes. It was found that a total of 55 differential expression genes (DEGs) encoding 28 enzymes function in carbon flow to fatty acids of storage TAG. Most of the DEGs encoding above enzymes showed similar expression pattern, indicating the DEGs are cooperatively involved in carbon flow into fatty acids. In addition, 41 DEGs associated with signal transductions, transport and metabolic processing of auxin, gibberellin, abscisic acid, cytokinin and salicylic acids were found in the RNA-Seq database, which indicates the important roles of the phytohormones in controlling embryo development and fatty acids synthesis. 122 DEGs encoding transcriptional factor family members were found in developing canola embryos. Furthermore, BnDOF5.6, a zinc finger transcriptional factor gene, found in RNA-Seq database was down-regulated in developing canola embryos. The transgenic plants displayed reduced embryo sizes, decreased fatty acids contents and altered seed fatty acids composition in canola. Down-regulated of BnDof5.6 also changed the expression levels of genes involved in fatty acids synthesis and desaturation. Our results indicate that BnDof5.6 is required for embryo development and fatty acids synthesis in canola. Overall this study presents new information on the global expression patterns of genes during embryo development and will expand our understanding of the complex molecular mechanism of carbon flow into fatty acids and embryo development in canola.

  9. Synthesis, structure, and cooperative proton-electron transfer reaction of Bis(5,6-diethylpyrazinedithiolato)metal complexes (M = Ni, Pd, Pt).

    PubMed

    Kubo, Takashi; Ohashi, Misako; Miyazaki, Katsuaki; Ichimura, Akio; Nakasuji, Kazuhiro

    2004-11-15

    New proton and electron donors, M(II)(HL)(2) (M = Ni, Pd, Pt; L = 5,6-diethylpyradzinedithiolate), as well as a proton and electron acceptor, Pt(IV)(L)(2), were prepared and characterized. The pH-dependent cyclic voltammetry of the M(II)(HL)(2) complexes revealed a favorable Gibbs free energy (K(com) > 1) for the proton and electron transfer reactions from M(II)(HL)(2) to M(IV)(L)(2); i.e., the equilibrium for the following reaction lies to the right: M(II)(HL)(2) + M(IV)(L)(2) <==>2M(III)(HL)(L).

  10. Shen-Kang protects 5/6 nephrectomized rats against renal injury by reducing oxidative stress through the MAPK signaling pathways

    PubMed Central

    LIU, MEIYOU; PARK, JISOO; WU, XIAOXIAO; LI, YUWEN; TRAN, QUANGDON; MUN, KISUN; LEE, YONGJIN; HUR, GANG MIN; WEN, AIDONG; PARK, JONGSUN

    2015-01-01

    Chronic kidney disease (CKD) is a worldwide public health concern with limited treatment options. The incidence of CDK is increasing and the disease is associated with a poor quality of life and a high financial cost of treatment. Shen-Kang (SK), a traditional Chinese herbal medicine, has been used clinically in the treatment of renal diseases for decades. This study was carried out to validate the therapeutic effects of SK on renal injury induced by 5/6 nephrectomy, as well as its effects on the apoptosis of proximal tubule epithelial cells (HK-2 cells), in an aim to elucidate its mechanisms of action. For this purpose, an animal model of renal injury was created by subjecting rats to a 5/6 nephrectomy. The rats in the sham-operated and model groups received distilled water, while the rats in the SK and enalapril (EN) groups were treated with SK or EN. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were measured. Kidney tissues obtained from the rats were stained with hematoxylin and eosin. HK-2 cells were employed to investigate the effects of SK on the apoptosis of renal proximal tubule epithelial cells induced by treatment with hydrogen peroxide (H2O2). In addition, cell viability was measured by MTT assay. Apoptotic events were monitored by western blot analysis, flow cytometric analysis and nuclear morphological anlaysis. The levels of intracellular reactive oxygen species (ROS) were measured by flow cytometric analysis with dihydroethidium staining. The results revealed that the administration of SK to 5/6 nephrectomized rats for 1 week significantly decreased the levels of SCr and BUN. The morphological observations of the kidneys also indicated the amelioration of damage to renal tissue. Treatment of the HK-2 cells with SK significantly protected the cells from H2O2-induced apoptosis, as indicated by an increase in cell viability, the decrease in the cleavage of poly(ADP-ribose) polymerase (PARP) and fewer condensed nuclei. H2O2-induced

  11. Lasing of multiperiod quantum-cascade lasers in the spectral range of (5.6–5.8)-μm under current pumping

    SciTech Connect

    Egorov, A. Yu. Babichev, A. V.; Karachinsky, L. Ya.; Novikov, I. I.; Nikitina, E. V.; Tchernycheva, M.; Sofronov, A. N.; Firsov, D. A.; Vorobjev, L. E.; Pikhtin, N. A.; Tarasov, I. S.

    2015-11-15

    The lasing of multiperiod quantum-cascade lasers in the spectral range of (5.6–5.8)-μm under current pumping are demonstrated. The quantum-cascade laser heterostructure is grown by molecular-beam epitaxy technique. Despite the relatively short laser cavity length and high level of external loss the laser shows the lasing in the temperature range of 80–220 K. The threshold current density below 4 kA/cm{sup 2} at 220 K with the characteristic temperature T{sub 0} = 123 K was demonstrated.

  12. Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid.

    PubMed

    Stansfield, Ian; Avolio, Salvatore; Colarusso, Stefania; Gennari, Nadia; Narjes, Frank; Pacini, Barbara; Ponzi, Simona; Harper, Steven

    2004-10-18

    5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series.

  13. Cr:ZnS laser-pumped subharmonic GaAs optical parametric oscillator with the spectrum spanning 3.6-5.6  μm.

    PubMed

    Smolski, V O; Vasilyev, S; Schunemann, P G; Mirov, S B; Vodopyanov, K L

    2015-06-15

    Using a subharmonic optical parametric oscillator (OPO) based on orientation-patterned GaAs, we produced a broadband instantaneous output that spans 3.6-5.6 μm at 50-dB level (4.4-5.2 μm at 3 dB level), has 110 mW of average power, and is suitable for producing wideband-frequency combs in the mid-infrared. The OPO was synchronously pumped by a compact Kerr-lens mode-locked femtosecond Cr:ZnS oscillator with the central wavelength 2.38 μm and pulse repetition frequency 175 MHz.

  14. Facile synthesis of 4,5,6a,7-tetrahydrodibenzo[de,g]chromene heterocycles and their transformation to phenanthrene alkaloids

    PubMed Central

    Kapadia, Nirav; Harding, Wayne

    2013-01-01

    Oxa-Pictet-Spengler cyclization and microwave-assisted C-H arylation have been implemented as key steps in the synthesis of new isochroman heterocycles containing a 4,5,6a,7-tetrahydrodibenzo[de,g]chromene motif. These isochromans may be easily transformed to phenanthrene alkaloids via acidic cleavage of the isochroman ring and standard synthetic manipulations thereafter. The route described is attractive in that it provides access to two biologically interesting scaffolds in simple and high yielding synthetic steps. PMID:24187388

  15. Crystal structure of 2-amino-7,7-dimethyl-5-oxo-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4 H-chromene-3-carbonitrile hemihydrate

    NASA Astrophysics Data System (ADS)

    Sharma, N.; Banerjee, B.; Brahmachari, G.; Kant, R.; Gupta, V. K.

    2015-12-01

    The title compound, 2-amino-7,7-dimethyl-5-oxo-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4 Hchromene-3-carbonitrile was synthesized by multicomponent reaction at room temperature using commercially available urea as inexpensive and environmentally benign organo-catalyst. Its structure was determined by X-ray structure analysis. The crystals are monoclinic, sp. gr. C2/ c, a = 22.010(6), b = 11.0364(10), c = 17.147(4) Å, β = 130.37(4)°, Z = 8, R = 0.0433 for 2377 observed reflections.

  16. A new and practical method for the synthesis of 6-aryl-5,6-dihydropyrido[2,3-[Formula: see text

    PubMed

    Camarasa, Marta; Barnils, Christian; Puig de la Bellacasa, Raimon; Teixidó, Jordi; Borrell, José I

    2013-08-01

    A one step general synthetic methodology for the synthesis of 6-aryl-5,6-dihydropyrido[2,3-d]pyrimidine-4,7(3H,8H)-diones (17{[Formula: see text]} ([Formula: see text]) and 20{[Formula: see text]} ([Formula: see text])) is described. This methodology is based on reacting a 2-aryl-substituted acrylate (16{[Formula: see text]}) with the corresponding 6-aminopyrimidin-4(3[Formula: see text]-one (13 ([Formula: see text]; 19 ([Formula: see text])) in presence of a base under microwave irradiation. The resulting pyrido[2,3-[Formula: see text

  17. A Tax for Higher Education

    ERIC Educational Resources Information Center

    Blumenstyk, Goldie

    2012-01-01

    Higher education pays off handsomely for society. Yet on a nationwide basis, states' support for higher education per full-time-equivalent student has fallen to just $6,290, the lowest in 15 years. A dedicated source of funds for higher education is problematic. But what if state and federal lawmakers applied the impeccable logic of the gas tax to…

  18. Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site.

    PubMed

    Tomašič, Tihomir; Katsamakas, Sotirios; Hodnik, Žiga; Ilaš, Janez; Brvar, Matjaž; Solmajer, Tom; Montalvão, Sofia; Tammela, Päivi; Banjanac, Mihailo; Ergović, Gabrijela; Anderluh, Marko; Peterlin Mašič, Lucija; Kikelj, Danijel

    2015-07-23

    Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coli DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coli DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coli topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and ΔtolC E. coli strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

  19. Poly[hexa-aqua-(μ9-cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ato)trimanganese(II)].

    PubMed

    Sun, Weixuan; Zang, Hu; Quan, Chengshi

    2013-01-01

    The asymmetric unit of the title compound, [Mn3(C12H6O12)(H2O)6] n , comprises one Mn(II) ion, one third of a cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ate anion and two aqua ligands. The anion is completed by application of a -3 axis. The Mn(II) ion is six-coordinated by six O atoms from two aqua ligands and three different cyclo-hexa-carboxyl-ate anions in an octa-hedral geometry. The six carboxyl-ate groups adopt a bridging bidentate mode to ligate the Mn(II) ions. Thus, each cyclo-hexane-1,2,3,4,5,6-hexa-carboxyl-ate anion adopts a μ9-connected mode, ligating nine different Mn(II) ions and forming a three-dimensional framework. In the framework, there are strong O-H⋯O hydrogen-bonding inter-actions, which further stabilize the crystal structure.

  20. Genetics and molecular mapping of resistance to Plasmodiophora brassicae pathotypes 2, 3, 5, 6, and 8 in rutabaga (Brassica napus var. napobrassica).

    PubMed

    Hasan, Muhammad Jakir; Rahman, Habibur

    2016-10-01

    Clubroot disease, caused by Plasmodiophora brassicae, is a threat to the production of Brassica crops including oilseed B. napus. In Canada, several pathotypes of this pathogen, such as pathotypes 2, 3, 5, 6, and 8, were identified, and resistance to these pathotypes was found in a rutabaga (B. napus var. napobrassica) genotype. In this paper, we report the genetic basis and molecular mapping of this resistance by use of F2, backcross (BC1), and doubled haploid (DH) populations generated from crossing of this rutabaga line to a susceptible spring B. napus canola line. The F1, F2, and BC1 populations were evaluated for resistance to pathotype 3, and the DH population was evaluated for resistance to pathotypes 2, 3, 5, 6, and 8. A 3:1 segregation in F2 and a 1:1 segregation in BC1 were found for resistance to pathotype 3, and a 1:1 segregation was found in the DH population for resistance to all pathotypes. Molecular mapping by using the DH population identified a genomic region on chromosome A8 carrying resistance to all five pathotypes. This suggests that a single gene or a cluster of genes, located in this genomic region, is involved in the control of resistance to these pathotypes.

  1. Microscale synthesis of isotopically labeled R-[6-xH]N5,N10-methylene-5,6,7,8-tetrahydrofolate as a cofactor for thymidylate synthase.

    PubMed

    Agrawal, Nitish; Mihai, Cornelia; Kohen, Amnon

    2004-05-01

    A one-pot synthesis of isotopically labeled R-[6-xH]N5,N10-methylene-5,6,7,8-tetrahydrofolate (CH2H4F) is presented, where x=1, 2, or 3 represents hydrogen, deuterium, or tritium, respectively. The current procedure offers high-yield, high-purity, and microscale-quantity synthesis. In this procedure, two enzymes were used simultaneously in the reaction mixture. The first was Thermoanaerobium brockii alcohol dehydrogenase, which stereospecifically catalyzed a hydride transfer from C-2-labeled isopropanol to the re face of oxidized nicotinamide adenine dinucleotide phosphate to form R-[4-xH]-labeled reduced nicotinamide adenine dinucleotide phosphate. The second enzyme, Escherichia coli dihydrofolate reductase, used the xH to reduce 7,8-dihydrofolate (H2F) to form S-[6-xH]5,6,7,8-tetrahydrofolate (S-[6-xH]H4F). The enzymatic reactions were followed by chemical trapping of S-[6-xH]H4F with formaldehyde to form the final product. Product purification was carried out in a single step by reverse phase high-pressure liquid chromatography separation followed by lyophilization. Two analytical methods were developed to follow the reaction progress. Finally, the utility of the labeled cofactor in mechanistic studies of thymidylate synthase is demonstrated by measuring the tritium kinetic isotope effect on the enzyme's second order rate constant.

  2. Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method.

    PubMed

    Ito, Shosuke; Kikuta, Marina; Koike, Shota; Szewczyk, Grzegorz; Sarna, Michal; Zadlo, Andrzej; Sarna, Tadeusz; Wakamatsu, Kazumasa

    2016-05-01

    Eumelanin photoprotects pigmented tissues from ultraviolet (UV) damage. However, UVA-induced tanning seems to result from the photooxidation of preexisting melanin and does not contribute to photoprotection. We investigated the mechanism of UVA-induced degradation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-melanin taking advantage of its solubility in a neutral buffer and using a differential spectrophotometric method to detect subtle changes in its structure. Our methodology is suitable for examining the effects of various agents that interact with reactive oxygen species (ROS) to determine how ROS is involved in the UVA-induced oxidative modifications. The results show that UVA radiation induces the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in eumelanin, which is then cleaved to form a photodegraded, pyrrolic moiety and finally to form free pyrrole-2,3,5-tricarboxylic acid. The possible involvement of superoxide radical and singlet oxygen in the oxidation was suggested. The generation and quenching of singlet oxygen by DHICA-melanin was confirmed by direct measurements of singlet oxygen phosphorescence.

  3. Synthesis and evaluation of 7-substituted-5,6-dihydrobenzo[c]acridine derivatives as new c-KIT promoter G-quadruplex binding ligands.

    PubMed

    Guo, Qian-Liang; Su, Hua-Fei; Wang, Ning; Liao, Sheng-Rong; Lu, Yu-Ting; Ou, Tian-Miao; Tan, Jia-Heng; Li, Ding; Huang, Zhi-Shu

    2017-04-21

    It has been shown that treatment of cancer cells with c-KIT G-quadruplex binding ligands can reduce their c-KIT expression levels thus inhibiting cell proliferation and inducing cell apoptosis. Herein, a series of new 7-substituted-5,6-dihydrobenzo[c]acridine derivatives were designed and synthesized. Subsequent biophysical evaluation demonstrated that the derivatives could effectively bind to and stabilize c-KIT G-quadruplex with good selectivity against duplex DNA. It was found that 12-N-methylated derivatives with a positive charge introduced at 12-position of 5,6-dihydrobenzo[c]acridine ring had similar binding affinity but lower stabilizing ability to c-KIT G-quadruplex DNA, compared with those of nonmethylated derivatives. Further molecular modeling studies showed possible binding modes of G-quadruplex with the ligands. RT-PCR assay and Western blot showed that compound 2b suppressed transcription and translation of c-KIT gene in K562 cells, which was consistent with the property of an effective G-quadruplex binding ligand targeting c-KIT oncogene promoter. Further biological evaluation showed that compound 2b could induce apoptosis through activation of the caspase-3 cascade pathway.

  4. Protective Effects of Bu-Shen-Huo-Xue Formula against 5/6 Nephrectomy-Induced Chronic Renal Failure in Rats

    PubMed Central

    Lu, Jian-Rao; Han, Hai-Yan; Chen, Jie; Xiong, Chong-Xiang; Wang, Xin-Hua; Hu, Jing; Chen, Xiu-Feng; Ma, Li

    2014-01-01

    Chronic renal failure (CRF) is a serious disease related to increasing incidence and prevalence as well as decline in quality of life. Bu-Shen-Huo-Xue formula (BSHX), one of traditional herbal formulations, has been clinically employed to treat CRF for decades, but the mechanisms involved have not been investigated. In the present study, we investigated the effects of BSHX on some closely related parameters in 5/6 nephrectomy CRF rats. Rats with CRF were divided into five groups, namely, one control group, one enalapril group, and three BSHX treatment groups (0.25, 0.5, and 1 g/kg·d). The rats subjected to sham operation were used as a normal control. After eight weeks of treatment, BSHX significantly decreased the levels of Scr and BUN, downregulated the mRNA expression levels of TGF-β1, CTGF, NF-κB, TNF-α, and OPN, upregulated the mRNA expression of PPARγ, and reduced in situ expression of fibronectin and laminins. Histological findings also showed significant amelioration of the damaged renal tissue. BSHX protects 5/6 nephrectomy rats against chronic renal failure probably via regulating the expression of TNF-α, NF-κB, TGF-β1, CTGF, PPARγ, OPN, fibronectin, and laminins and is useful for therapy of CRF. PMID:24864155

  5. Amination of the pyridinium cations in betaines. Synthesis of substituted pyrimido(5,6-c)-1'-azaquinolizine and its dihydro analogs

    SciTech Connect

    Kochkanyan, R.O.; Lukanyuk, S.S.

    1987-11-01

    The pyridinium cations within betaines can be aminated under mild conditions with aqueous ammonia, ultimately undergoing cyclization to a new tricyclic system: 4-substituted-3,5-dioxopyrimido(5,6-c)-1'-azaquinolizine. Intermediates in the reaction are 4-substituted-3,5-dioxo-2,2-dihydropyrimido(5,6-c)-6H-1'-quinolizines. Formation of the methylene group is coupled with transfer of an atom of hydrogen or deuterium from the ..cap alpha..-carbon of the dihydropyridine in compound II to the carbon atom of the azomethine group. The NMR spectrum is represented by the methylene proton signal (3.96 ppm) and by the multiplets of the pyridine and phenyl protons centered at 7.63 and 6.38 ppm respectively. Upon chloranil oxidation, and upfield shift of the pyridine protons is observed: the ..cap alpha..-proton forms a doublet (10.05 ppm, J= 6 Hz), the ..beta..-protons form a doublet and a triplet with centers at 8.57 (J = 8 Hz) and 8.22 (J = 7 Hz) ppm respectively, and the ..gamma..-proton forms a triplet at 8.8 (J = 7 Hz) ppm.

  6. Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro(and thieno)[2, 3-b]-quinolines, and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo(and thieno)-[2, 3-b]pyridines.

    PubMed

    Marco, José L; De Los Ríos, Cristóbal; Carreiras, María C; Baños, Josep E; Badia, Albert; Vivas, Nuria M

    2002-07-01

    The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities of a series of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro[2, 3-b]quinolines (10-12)/4-amino-5, 6, 7, 8-tetrahydro-2, 3-diphenylthieno[2, 3-b]quinoline (14) and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo[2, 3-b]pyridine (13)/4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-phenylcyclohepta[e]thieno[2, 3-b]pyridine (15) are described. These compounds are tacrine (THA) analogues which have been prepared either from readily available 2-amino-3-cyano-4, 5-diarylfurans (16-18) or from 2-amino-3-cyano-4, 5-diphenylthiophene (19), via Friedländer condensation with cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for acetylcholinesterase, the more potent being compound (13) which is three-fold less active than tacrine. The butyrylcholinesterase inhibition activity is significant only in compounds 10 and133, which are ten-fold less active than tacrine. It is found that the products 11 and 12 strongly inhibit acetylcholinesterase, and show excellent selectivity regarding butyrylcholinesterase.

  7. Crystal structure of 5-(5,6-di-hydro-benzo[4,5]imidazo[1,2-c]quinazolin-6-yl)-2-meth-oxy-phenol.

    PubMed

    Adam, Farook; Arafath, Md Azharul; Rosenani, A Haque; Razali, Mohd R

    2015-12-01

    In the mol-ecule of the title compound, C21H17N3O2, the 5,6-di-hydro-benzimidazo[1,2-c]quinazoline moiety is disordered over two orientations about a pseudo-mirror plane, with a refined occupancy ratio of 0.863 (2):0.137 (2). The dihedral angles formed by the benzimidazole ring system and the benzene ring of the quinazoline group are 14.28 (5) and 4.7 (3)° for the major and minor disorder components, respectively. An intra-molecular O-H⋯O hydrogen bond is present. In the crystal, mol-ecules are linked by O-H⋯N hydrogen bonds, forming chains running parallel to [10-1].

  8. Crystal structure and physicochemical characterization of 3β-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester

    NASA Astrophysics Data System (ADS)

    Fu, Jing; Dong, Xiaoxv; Yin, Xinbing; Cao, Sali; Yang, Chunjing; He, Huyiligeqi; Ni, Jian

    2017-02-01

    3β-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (T-OA) is a newly discovered potential antitumor compound. However, the poor solubility of T-OA leads to poor dissolution and limited clinical application. So as to enhance the dissolution and bioavailability of T-OA, an investigation of the polymorphism of T-OA was successfully undertaken. A new solvate and an amorphous form of T-OA were discovered through a comprehensive polymorph screening experiments. Their structures were elucidated by single-crystal structure analysis and extensively characterized by PXRD, DSC and SEM. The powder dissolution rates were compared with those of the previously known polymorph. Thermodynamic stability and phase transformation are also discussed in detail.

  9. Sparfloxacin charge transfer complexes with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and tetracyanoquinodimethane: Molecular structures, spectral, and DFT studies

    NASA Astrophysics Data System (ADS)

    Shehab, Ola R.; Mansour, Ahmed M.

    2015-08-01

    A simple, sensitive and rapid method was developed for the quantitative analysis of sparfloxacin in its pharmaceutical formulations through the formation of charge transfer complexes with π-acceptor systems. The Lambert-Beer's law was obeyed in the concentration ranges of 7-70 and 10-50 μg/mL sparfloxacin for 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and tetracyanoquinodimethane. Structural characterization of the isolated solid CT complexes was carried out by IR, 1H NMR, UV-Vis. and MS. The experimental studies were complemented by quantum chemical calculations at DFT level of theory. The electronic structures were investigated by TD-DFT calculations. Natural bond orbital analysis and molecular electrostatic potential maps were helpful in assigning the CT route. The formation constant, molar extinction coefficient, oscillator strength, dipole moment, standard free energy and ionization potential were calculated.

  10. 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis.

    PubMed

    Koch, Uwe; Attenni, Barbara; Malancona, Savina; Colarusso, Stefania; Conte, Immacolata; Di Filippo, Marcello; Harper, Steven; Pacini, Barbara; Giomini, Claudia; Thomas, Steven; Incitti, Ilario; Tomei, Licia; De Francesco, Raffaele; Altamura, Sergio; Matassa, Victor G; Narjes, Frank

    2006-03-09

    Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 microM), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

  11. Identification of 3,5,6-substituted indolin-2-one's inhibitors of Aurora B by development of a luminescent kinase assay.

    PubMed

    Zhang, Leilei; Yang, Tianming; Xie, Xilei; Liu, Gang

    2015-08-01

    Aurora B kinase plays an important role in the cell normal mitosis and overexpresses in a variety of tumors. Inhibition of Aurora B kinase resulted in an apoptosis of cancer cells, which prevented tumor growth in xenograft models. In this Letter, we developed a luminescent kinase assay to perform high-throughput screening for identification of small molecule Aurora B inhibitors. Two 3,5,6-substituted indolin-2-one derivatives were identified within an in-house compound library. Their new derivatives were then designed and synthesized that resulting two new inhibitors of Aurora B kinase with improved potency. Docking simulation further demonstrated the proposed binding modes between indolin-2-one inhibitor and Aurora B.

  12. Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as γ-secretase modulators (Part 2).

    PubMed

    Takai, Takafumi; Koike, Tatsuki; Nakamura, Minoru; Kajita, Yuichi; Yamashita, Toshiro; Taya, Naohiro; Tsukamoto, Tetsuya; Watanabe, Tomomichi; Murakami, Koji; Igari, Tomoko; Kamata, Makoto

    2016-07-15

    γ-Secretase modulators (GSMs), which lower pathogenic amyloid beta (Aβ) without affecting the production of total Aβ or Notch signal, have emerged as a potential therapeutic agent for Alzheimer's disease (AD). A novel series of 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives was discovered and characterized as GSMs. Optimization of substituents at the 8-position of the core scaffold using ligand-lipophilicity efficiency (LLE) as a drug-likeness guideline led to identification of various types of high-LLE GSMs. Phenoxy compound (R)-17 exhibited especially high LLE as well as potent in vivo Aβ42-lowering effect by single administration. Furthermore, multiple oral administration of (R)-17 significantly reduced soluble and insoluble brain Aβ42, and ameliorated cognitive deficit in novel object recognition test (NORT) using Tg2576 mice as an AD model.

  13. High-efficiency blue electroluminescence based on coumarin derivative 3-(4-(anthracen-10-yl)phenyl)-benzo[5,6]coumarin.

    PubMed

    Zhang, Hui; Chai, Haifang; Yu, Tianzhi; Zhao, Yuling; Fan, Duowang

    2012-11-01

    The electroluminescent (EL) properties of a new coumarin derivative, 3-(4-(anthracen-10-yl)phenyl)-benzo[5,6]coumarin (APBC), were investigated. The results show that the EL devices comprised of vacuum vapor-deposited films using the derivative as dopant exhibited blue emission that is identical to the photoluminescence of the thin film. The electroluminescence device of ITO/2-TNATA (5 nm)/NPB (40 nm)/CBP : APBC (1.0 wt%, 30 nm)/PBD (30 nm)/LiF (1 nm)/Al (100 nm) gives a maximum luminous efficiency of 2.3 cd/A at the current density of 20 mA/cm(2), and maximum luminance of 5169 cd/m(2) at 16 V. The external quantum efficiency of the device is 1.85 %.

  14. Cross sections for K-shell ionization of atoms induced by 1.5-6.0 MeV 4He ions

    NASA Astrophysics Data System (ADS)

    Lin, E. K.; Wang, C. W.; Yu, Y. C.; Chuang, F. T.; Huang, Y. M.

    1992-12-01

    K-shell X-ray production cross sections have been measured for elements of Ti, Mn, Co, Ni, Cu, Zn and Ga (Z = 22-31) using 4He-ion beams in the energy range 1.5-6.0 MeV. Results are compared with the predictions of the first-order Born approximation (FOBORN) and the energy-loss Coulomb-deflection perturbed-stationary-state relativistic theory (ECPSSR), and those of earlier measurements. The agreement with the ECPSSR theory is within 10%. In addition to the experimental cross sections, the Kβ/Kα X-ray yield ratios have been extracted, and compared with the calculated values of Scofield, and the "recommended" values of Khan and Karimi.

  15. Measurement of G(E(p))/G(M(p)) in e(-->)p---> e(-->)p to Q(2) = 5.6 GeV(2).

    PubMed

    Gayou, O; Aniol, K A; Averett, T; Benmokhtar, F; Bertozzi, W; Bimbot, L; Brash, E J; Calarco, J R; Cavata, C; Chai, Z; Chang, C-C; Chang, T; Chen, J-P; Chudakov, E; De Leo, R; Dieterich, S; Endres, R; Epstein, M B; Escoffier, S; Fissum, K G; Fonvieille, H; Frullani, S; Gao, J; Garibaldi, F; Gilad, S; Gilman, R; Glamazdin, A; Glashausser, C; Gomez, J; Gorbenko, V; Hansen, J-O; Higinbotham, D W; Huber, G M; Iodice, M; de Jager, C W; Jiang, X; Jones, M K; Kelly, J J; Khandaker, M; Kozlov, A; Kramer, K M; Kumbartzki, G; LeRose, J J; Lhuillier, D; Lindgren, R A; Liyanage, N; Lolos, G J; Margaziotis, D J; Marie, F; Markowitz, P; McCormick, K; Michaels, R; Milbrath, B D; Nanda, S K; Neyret, D; Papandreou, Z; Pentchev, L; Perdrisat, C F; Piskunov, N M; Punjabi, V; Pussieux, T; Quéméner, G; Ransome, R D; Raue, B A; Roché, R; Rvachev, M; Saha, A; Salgado, C; Sirca, S; Sitnik, I; Strauch, S; Todor, L; Tomasi-Gustafsson, E; Urciuoli, G M; Voskanyan, H; Wijesooriya, K; Wojtsekhowski, B B; Zheng, X; Zhu, L

    2002-03-04

    The ratio of the electric and magnetic form factors of the proton G(E(p))/G(M(p)), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic e(-->)p---> e(-->)p reaction. The new data presented span the range 3.5< Q(2)< 5.6 GeV(2) and are well described by a linear Q(2) fit. Also, the ratio sqrt[Q(2)] F(2(p))/F(1(p)) reaches a constant value above Q(2) = 2 GeV(2).

  16. Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

    PubMed Central

    Cuschieri, K.; de Koning, M. N. C.; van Doorn, L. J.; Snijders, P. J. F.; Meijer, C. J. L. M.; Quint, W. G. V.; Arbyn, M.

    2014-01-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, “enriched” with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening. PMID:25210073

  17. DFT versus Møller-Plesset conformational profile and vibrational assignments of non- planar phenoxyacetic acid and 2,3,4,5,6-pentafluorophenoxyacetic acid

    NASA Astrophysics Data System (ADS)

    Badawi, Hassan M.

    2010-08-01

    The structural stability of phenoxyacetic acid and 2,3,4,5,6-pentafluorphenoxyacetic acid was investigated by the DFT-B3LYP and the ab initio MP2 calculations with the 6-311G ** basis set. For the parent acid the calculations were extended to the MP4(SDQ) level of theory. At the DFT-B3LYP level of calculation the planar Tttp ( transoid O dbnd C sbnd O sbnd H) was predicted to be about 0.5 and 1.3 kcal/mol lower in energy than the non-planar Cgcpp and Tgcpp ( cisoid O dbnd C sbnd O sbnd H) forms, respectively. At the MP2 and the MP4(SDQ) levels the Cgcpp form was predicted to be about 0.8 and 1.4 kcal/mol lower in energy than the Tgcpp and the Tttcp structures, respectively. On the basis of the Møller-Plesset calculations the Cgcpp and the Tgcpp conformations were adopted as the low and high energy structures of phenoxyacetic acid. The observed spectral intensities of phenoxyacetic acid were consistence with the Cgcpp conformation being the predominant form of the acid at room temperature. At the DFT and MP2 levels of theory 2,3,4,5,6-pentafluorophenoxyacetic acid was predicted to exist predominantly in the Cgcpp structure. The vibrational wavenumbers were computed at the B3LYP level of theory and tentative vibrational assignments were provided on the basis of combined theoretical and experimental infrared and Raman data of both molecules.

  18. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

    PubMed Central

    Howat, William J; Blows, Fiona M; Provenzano, Elena; Brook, Mark N; Morris, Lorna; Gazinska, Patrycja; Johnson, Nicola; McDuffus, Leigh‐Anne; Miller, Jodi; Sawyer, Elinor J; Pinder, Sarah; van Deurzen, Carolien H M; Jones, Louise; Sironen, Reijo; Visscher, Daniel; Caldas, Carlos; Daley, Frances; Coulson, Penny; Broeks, Annegien; Sanders, Joyce; Wesseling, Jelle; Nevanlinna, Heli; Fagerholm, Rainer; Blomqvist, Carl; Heikkilä, Päivi; Ali, H Raza; Dawson, Sarah‐Jane; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli‐Matti; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W; Couch, Fergus J; Olson, Janet E; Devillee, Peter; Mesker, Wilma E; Seyaneve, Caroline M; Hollestelle, Antoinette; Benitez, Javier; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Bolla, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K; Pharoah, Paul D; Sherman, Mark E

    2014-01-01

    Abstract Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large‐scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65–70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose‐response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96–98%), but yielded many false positives (positive predictive value = 30–32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large‐scale, quantitative scoring of immunohistochemically stained tissue

  19. Sediment record of environmental change at Lake Lop Nur (Xinjiang, NW China) from 13.0 to 5.6 cal ka BP

    NASA Astrophysics Data System (ADS)

    Wang, Jingzhong; Jia, Hongjuan

    2016-09-01

    Lake Lop Nur is located in the eastern part of the Tarim Basin in Xinjiang, northwestern China. A 220-cm-long sediment core was collected from the center of the ear-shaped depression forming the basin and dated with AMS14C. Grain size, total organic matter (TOC), total nitrogen (TN), and TOC/TN (C/N) analyses were used to reconstruct climatic conditions from 13.0 to 5.6 cal ka BP. The results showed five main climatic stages. Zone I (13.0-11.3 cal ka BP) was a wet-dry environment, whereas Zone II (11.3-8.9 cal ka BP) consisted of a primarily wet environment. Zone III (8.9-7.7 cal ka BP) was subdivided into Zone IIIa (8.9-8.2 cal ka BP) that indicated lake constriction and dry climate, and Zone IIIb (8.2-7.7 cal ka BP) in which the proxies indicated wet conditions. In Zone IV (7.7-6.6 cal ka BP), the climate presented a bit wet conditions. In Zone V (6.6-5.6 cal ka BP), abundant glauberite is present in the sediment and silt dominates the lithology; these results indicate the lake shrank and the overall climate was dry. Abrupt environmental events were also identified, including six dry events at 11.0, 10.5, 9.3, 8.6, 8.2, and 7.6 cal ka BP and one flood event from 7.8 to 7.7 cal ka BP in the Early-Middle Holocene.

  20. Clinical evaluation of a GP5+/6+-based luminex assay having full high-risk human papillomavirus genotyping capability and an internal control.

    PubMed

    Geraets, D T; Cuschieri, K; de Koning, M N C; van Doorn, L J; Snijders, P J F; Meijer, C J L M; Quint, W G V; Arbyn, M

    2014-11-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥ 30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥ 30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.

  1. Synthesis of gamma- and delta-lactones from 1alpha-hydroxy-5,6-trans-vitamin D3 by ring-closing metathesis route and their reduction with metal hydrides.

    PubMed

    Wojtkielewicz, Agnieszka; Morzycki, Jacek W

    2007-06-01

    New synthetic pathway towards 19-functionalized derivatives of 1alpha-hydroxy-5,6-trans-vitamin D3 was described. Ring-closing metathesis (RCM) of 1alpha-hydroxy-5,6-trans-vitamin D3 1-omega-alkenoates was a key-step. Hydride reduction of resulting lactones led to the new vitamin D3 analogues.

  2. Combination of a higher-tier flow-through system and population modeling to assess the effects of time-variable exposure of isoproturon on the green algae Desmodesmus subspicatus and Pseudokirchneriella subcapitata.

    PubMed

    Weber, Denis; Schaefer, Dieter; Dorgerloh, Michael; Bruns, Eric; Goerlitz, Gerhard; Hammel, Klaus; Preuss, Thomas G; Ratte, Hans Toni

    2012-04-01

    A flow-through system was developed to investigate the effects of time-variable exposure of pesticides on algae. A recently developed algae population model was used for simulations supported and verified by laboratory experiments. Flow-through studies with Desmodesmus subspicatus and Pseudokirchneriella subcapitata under time-variable exposure to isoproturon were performed, in which the exposure patterns were based on the results of FOrum for Co-ordination of pesticide fate models and their USe (FOCUS) model calculations for typical exposure situations via runoff or drain flow. Different types of pulsed exposure events were realized, including a whole range of repeated pulsed and steep peaks as well as periods of constant exposure. Both species recovered quickly in terms of growth from short-term exposure and according to substance dissipation from the system. Even at a peak 10 times the maximum predicted environmental concentration of isoproturon, only transient effects occurred on algae populations. No modified sensitivity or reduced growth was observed after repeated exposure. Model predictions of algal growth in the flow-through tests agreed well with the experimental data. The experimental boundary conditions and the physiological properties of the algae were used as the only model input. No calibration or parameter fitting was necessary. The combination of the flow-through experiments with the algae population model was revealed to be a powerful tool for the assessment of pulsed exposure on algae. It allowed investigating the growth reduction and recovery potential of algae after complex exposure, which is not possible with standard laboratory experiments alone. The results of the combined approach confirm the beneficial use of population models as supporting tools in higher-tier risk assessments of pesticides.

  3. Synthesis, antitumor, and DNA binding behavior of novel 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5, 6 dihydropyrimidin derivatives in aqueous medium.

    PubMed

    Lamani, Devappa S; Reddy, K R Venugopala; Naik, H S Bhojya; Pai, K S R; Kumar, Ravishankar; Naik, H R Prakash; Naik, L R

    2010-08-01

    This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a-f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a-f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, (1)HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evaluated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K(b)) observed 4.3 x 10(5) M(-1) for (2a), and 3.8 x 10(5) M(-1) for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).

  4. Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity.

    PubMed

    Šarlauskas, Jonas; Pečiukaitytė-Alksnė, Milda; Misevičienė, Lina; Marozienė, Audronė; Polmickaitė, Evelina; Staniulytė, Zita; Čėnas, Narimantas; Anusevičius, Žilvinas

    2016-01-15

    Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones (NPDOs), a new type of N-heterocycle-fused o-quinones, have been synthesized. They have been found to be efficient electron-accepting substrates of NADPH-dependent single-electron-transferring P-450R and two-electron transferring NQO1, generating reactive oxygen species (ROS) with a concomitant decrease in NADPH, which is consistent with redox-cycling. The reactivity of NPDOs toward P-450R (in terms of kcat/Km) varied in the range of 10(6)-10(7)M(-1)s(-1), while their reduction by NQO1 proceeded much faster, approaching the diffusion control limit (kcat/Km∼10(8)-10(9)M(-1)s(-1)). NPDOs exhibited relatively high cytotoxic activity against human lung carcinoma (A-549) and breast tumor (MCF-7) cell lines (LC50=0.1-8.3μM), while promyelocytic leukemia cells (HL-60) were less sensitive to NPDOs (LC50⩾10μM). 3-Nitro-substituted NPDO (11) revealed the highest potency against both A-549 and MCF-7 cell lines, with LC50 of 0.12±0.03μM and 0.28±0.08μM, respectively. Dicoumarol partly suppressed the activity of the compounds against A-594 and MCF-7 cell lines, suggesting that their cytotoxic action might be partially influenced by NQO1-mediated bioreductive activation.

  5. New 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines: synthesis and computational study.

    PubMed

    Kosychova, Lidija; Karalius, Antanas; Staniulytė, Zita; Sirutkaitis, Romualdas Aleksas; Palaima, Algirdas; Laurynėnas, Audrius; Anusevičius, Žilvinas

    2015-03-26

    Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3-nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, 1H- and 13C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring.

  6. Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition

    PubMed Central

    González, Beatriz; Baños-Sanz, Jose Ignacio; Villate, Maider; Brearley, Charles Alistair; Sanz-Aparicio, Julia

    2010-01-01

    Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates. PMID:20453199

  7. Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies.

    PubMed

    Khatri, Chetan K; Indalkar, Krishna S; Patil, Chandragouda R; Goyal, Sameer N; Chaturbhuj, Ganesh U

    2017-04-15

    A series of 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene derivatives were synthesized and evaluated for in vitro COX inhibitory potential. Within the series, compounds 4a, 4j, 4k, and 4q were identified as potential and selective COX-2 inhibitors with COX-2 IC50 in 0.31-1.40µM range; COX-2 selectivity index (SI)=48.8-183.8 range and they showed percent PGE-2 inhibitory activity in the range of 25.4-46.9. Further, compounds 4a, 4j, 4k and 4q displayed potent anti-inflammatory activity with percentage rise in paw volume ranging from 21.1-30.5 at 180min, while celecoxib demonstrated 19.6 percentage rise at the same dose at 180min in carrageenan-induced rat paw edema assay. Cell viability via MTT assay showed no cytotoxicity up to 80µM concentrations. Molecular docking study of potent compounds in the series showed Gscore comparable to celecoxib with similar binding orientation for the COX-2 active site which also corroborates the observed in vitro COX-2 inhibition.

  8. Physical localisation of the breakpoints of a constitutional translocation t(5;6)(q21;q21) in a child with bilateral Wilms' tumour.

    PubMed Central

    Hoban, P R; Cowen, R L; Mitchell, E L; Evans, D G; Kelly, M; Howard, P J; Heighway, J

    1997-01-01

    A 6 month old boy presented with bilateral Wilms' tumour. Cytogenetic analysis of the lymphocytes from the patient showed a de novo balanced translocation t(5;6)(q21;q21), which was also present in the tumour material as the sole cytogenetic abnormality. To facilitate the identification of the translocation breakpoints, we have established a lymphoblastoid cell line (MA214L) from the patient which maintains the translocation in culture. We have used Genethon microsatellite markers as sequence tagged sites (STSs) to isolate yeast artificial chromosome (YAC) clones to 5q and 6q from human genomic libraries. Using fluorescence in situ hybridisation (FISH) on metaphase preparations of MA214L, we have physically defined the translocation breakpoints between YAC clones on each chromosome arm. The genetic distance separating the flanking YACs on 6q21 is 3 cM, while that on 5q21 is 4 cM. To date this is the first report of these chromosomal regions being implicated in Wilms' tumourigenesis. Images PMID:9138163

  9. Efficient blue organic light-emitting diodes using N(2) ,N(2) ,N(11) ,N(11) ,5,6,7,8-octaphenyltriphenylene-2,11-diamine derivatives.

    PubMed

    Kim, Young Seok; Jeong, Su Jin; Lee, Hyun Woo; Kim, Jwajin; Lee, Song Eun; Kim, Young Kwan; Yoon, Seung Soo

    2016-06-01

    In this study, we have synthesized phenyl-substituted triphenylene derivatives, using the Diels-Alder reaction and the Buchwald-Hartwig reaction. To investigate electroluminescence properties of these materials, multilayer organic light-emitting diode (OLED) devices were fabricated with a structure of indium-tin-oxide (ITO) (180 nm)/4,4'-bis(N-(1-naphthyl)-N-phenylamino)biphenyl (NPB) (50 nm)/blue-emitting materials (1-3) (30 nm)/bathophenanthroline (Bphen) (35 nm)/lithium quinolate (Liq) (2 nm)/Al (100 nm). A device using N(2) ,N(2) ,N(11) ,N(11) ,5,6,7-heptaphenyltriphenylene-2,11-diamine (2) exhibited efficient blue emission with luminous, power, and external quantum efficiencies of 0.92 cd/A, 0.67 lm/W, and 1.17% at 20 mA/cm(2) , respectively. The Commission International de L'Éclairage coordinates of this device were (x = 0.15, y = 0.09) at 6.0 V. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Sensitive and selective determination of GSH based on the ECL quenching of Ru(II) 1,10-phenanthroline-5,6-dione complex.

    PubMed

    Xu, Yanxue; Zhang, Lei; Liu, Yuan; Jin, Zhaoyu; Zhao, Qian; Yang, Feng; Xiao, Dan

    2016-03-15

    Electrochemiluminescence (ECL) material Ru-dpq (Ru(bpy)2dpq(2+), dpq=1,10-phenanthroline-5,6-dione; bpy=2,2'-bipyridine) is found to be produced strong and stable anodic ECL signal, which could be quenched by reduced glutathione (GSH) and exhibits high sensitivity and selectivity simultaneously. According to the mass spectra of Ru-SG (product of Ru-dpq reacted with GSH), and single crystal structure of the final oxidized product Ru-dcbpy ((Ru(bpy)2dcbpy(2+), dcbpy=3,3-dicarboxy-2,2-bipyridine), we propose a new interacted mechanism between Ru-dpq and GSH. A good linear relation is estimated to be from 0.1 pM to 50 μM in the presence of calcium ion and the detection limit is as low as 0.087 pM (with the signal-to-noise ratio of 3). The relative standard deviation is 2.3% (for three repeated measurements). Furthermore, the ECL signal of Ru-dpq under a constant potential (1.2V) is extremely stable and the intensity could be maintained over 600 s, which promotes us to determine the concentration of GSH via chronoamperometry.

  11. A multichannel harpoon model for reactive quenching of Xe 5p/sup 5/6p by Cl/sub 2/

    SciTech Connect

    Bruce, M.R.; Layne, W.B.; Keto, J.W.

    1987-01-01

    A harpoon reaction model employing multiple crossings based on the formalism of Bauer et al and Gislason and Sachs is developed to explain the large cross sections (sigma approx.400 A/sup 2/) measured for the reaction Xe 5p/sup 5/6p + Cl/sub 2/. The model calculates the Landau-Zener transition probability for each intermediate ionic crossing with the covalent surface. The transition matrix elements are represented as a product of the electronic interaction (modeled by the empirical result of Olson et al) and a Frank-Condon factor for the Cl/sub 2/ ..-->.. Cl/sub 2//sup -/ transition. The model predicts near unit probability for a transition to the ionic surface for impact parameters less than 20 Bohr. Once transfer occurs, the pair is captured by dissociation of Cl/sub 2//sup -/ to form XeCl. The large temperature dependence observed qualitatively in the experiments is explained by the increased cross section for vibrationally excited Cl/sub 2/. A simple model for orbiting collisions is used to estimate the effect of termolecular collisions.

  12. Transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) causes DNA damage and triggers homologous recombination repair in mammalian cells.

    PubMed

    Stoimenov, Ivaylo; Gottipati, Ponnari; Schultz, Niklas; Helleday, Thomas

    2011-01-10

    Transcription, replication and homologous recombination are intrinsically connected and it is well established that an increase of transcription is associated with an increase in homologous recombination. Here, we have studied how homologous recombination is affected during transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a compound that prevents activating phosphorylations of the RNA Pol II C-terminal domain. We identify that DRB triggers an increase in homologous recombination within the hprt gene as well as increasing RAD51 foci formation in mammalian cells. Furthermore, we find that DRB-induced transcriptional stress is associated with formation of the nuclear foci of the phosphorylated form of H2AX (γH2AX). We accounted that about 72% of RAD51 foci co-localized with the observed γH2AX foci. Interestingly, we find that XRCC3 mutated, homologous recombination defective cells are hypersensitive to the toxic effect of DRB and fail to form RAD51 foci. In conclusion, we show that DRB-induced transcription inhibition is associated with the formation of a lesion that triggers RAD51-dependent homologous recombination repair, required for survival under transcriptional stress.

  13. Identification of two combined genes responsible for dechlorination of 3,5,6-trichloro-2-pyridinol (TCP) in Cupriavidus pauculus P2.

    PubMed

    Cao, Li; Xu, Jianhong; Wu, Guang; Li, Mingxing; Jiang, Jiandong; He, Jian; Li, Shunpeng; Hong, Qing

    2013-09-15

    Dehalogenation is an important mechanism for degrading and detoxifying halogenated aromatics in microbes. However, the biochemical and molecular mechanisms of dehalogenation of 3,5,6-trichloro-2-pyridinol (TCP) are still unknown. In this study, a novel 6012 bp gene cluster was cloned from TCP-degrading strain P2, which was responsible for the dehalogenation of TCP. The cluster included a monooxygenase gene (tcpA1), a flavin reductase gene (tcpB1), tcpR1, orf1 and orf2. TcpA1 and TcpB1 were indispensable for the dehalogenation of TCP. They worked together to catalyze the dehalogenation of three chlorine of TCP, and generated a more readily biodegradable product of 3,6-dihydroxypyridine-2,5-dione. TcpA1 displayed the highest activity against TCP at 40°C and at pH 8.0. Cu(2+), Zn(2+), and Hg(2+) significantly inhibited enzyme activity. To the best of our knowledge, this is the first report on a gene cluster responsible for TCP degradation.

  14. Synthesis of 6-N-R-Tetrazolo[1,5-c]quinazolin-5(6H)-ones and Their Anticancer Activity.

    PubMed

    Antypenko, Oleksii; Kovalenko, Sergiy; Rasulev, Bakhtiyor; Leszczynski, Jerzy

    2016-01-01

    Chemical compounds with tetrazole ring are very interesting systems that can be valuable in pharmaceutical and clinical applications, especially as anticancer agents. In this work, novel 6-N-R-tetrazolo[1,5-c]quinazolin-5(6H)-ones were synthesized. A large set of IR, LC-, EI-MS, 1H, 13C NMR and elemental analysis data were collected and evaluated for their structures and purity. Details of synthesis, namely the N-alkylation, are discussed, including reactions with secondary and tertiary amides. Four new synthesized compounds (2.7, 3.2, 5.2, 5.3) were tested in vitro for anticancer activity at 10 μM against 60 cell lines of nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. Further synthesis of substances within the series of substituted tetrazolo[1,5-c]quinazoline systems will be attempted to develop improved compounds with better anticancer activity.

  15. Syntheses, characterization and biological activities of rare earth metal complexes with curcumin and 1,10-phenanthroline-5,6-dione.

    PubMed

    Song, Yu-Min; Xu, Jun-Peng; Ding, Lan; Hou, Qian; Liu, Jing-Wang; Zhu, Zao-Long

    2009-03-01

    Three new solid complexes have been synthesized by the reaction of rare earth(III) nitrate with the first ligand curcumin (HL) and the second ligand 1,10-phenanthroline-5,6-dione (L') in alcohol solution (pH=6.5-7.0). The composition of the complexes has been characterized by elemental analysis, molar conductivity, thermogravimetric analysis, IR, UV-vis methods. The results reveal that beta-diketone group of the first ligand to coordinates with rare earth ions in bidentate mode after deprotonated. But the second ligand uses its two N atoms coordinates with rare earth ions in bidentate mode. The general formula of the complexes is REL(3)L' (RE=Sm, Eu, Dy). The results of antibacterial activity indicated that the complexes have excellent antibacterial ability for the testing bacterium than that of curcumin. The result of agarose gel electrophoresis suggested that the complex of SmL(3)L' can cleave the plasmid DNA at physiological pH and temperature. And it was found that the cleavage process of plasmid DNA was sensitive to pH, however, adding radical scavengers almost had no effect on the DNA cleavage reaction, therefore, the cleavage of DNA by SmL(3)L' does not produce diffusible hydroxyl radicals via the Fenton reaction.

  16. Negative Ion Chemical Ionization Mass Spectrometry for the Analysis of 3,5,6-trichloro-2-pyridinol in Saliva of Rats Exposed to Chlorpyrifos

    SciTech Connect

    Campbell, James A.; Timchalk, Chuck; Kousba, Ahmed A.; Wu, Hong; Valenzuela, Blandina R.; Hoppe, Eric W.

    2005-05-01

    Organophosphorus (OP) insecticides (e.g. chlorpyrifos) are widely used in a variety of applications, and the potential exists for significant occupational and environmental exposures. They have been associated with more occupational poisoning cases than any other class of insecticides. One of the best approaches for accurately assessing human dosimetry and determining risk from both occupational and environmental exposure is biomonitoring. Biological matrices such as blood and urine have been routinely used for biomonitoring; however, other matrices such as saliva represent a simple and readily obtainable fluid. As a result, saliva has been suggested as an alternative biological matrix for the evaluation of a broad range of biomarkers such as environmental contaminants, drugs of abuse, hormones, chemotherapeutics, heavy metals, and pesticides. Chlorpyrifos (CPF), and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCP), have been quantified in urine and blood as a biomarker for exposure to OP insecticides. The purpose of this study was to develop an analytical approach for detecting and quantitating the levels of TCP in saliva obtained from rats exposed to CPF and to evaluate the potential of saliva as a non-invasive biomonitoring matrix. Adult male rats were administered CPF, and blood and saliva were humanely collected for analysis of TCP and CPF. TCP was detected and quantitated in saliva using negative ion chemical ionization mass spectrometry with selected ion monitoring. Initial results indicate that saliva may be potentially utilized as a non-invasive biomonitoring matrix to determine exposure to organophosphate insecticides.

  17. An oral absorbent, surface-deacetylated chitin nano-fiber ameliorates renal injury and oxidative stress in 5/6 nephrectomized rats.

    PubMed

    Anraku, Makoto; Tabuchi, Ryo; Ifuku, Shinsuke; Nagae, Tomone; Iohara, Daisuke; Tomida, Hisao; Uekama, Kaneto; Maruyama, Toru; Miyamura, Shigeyuki; Hirayama, Fumitoshi; Otagiri, Masaki

    2017-04-01

    In this study, we report that surface-deacetylated chitin nano-fibers (SDACNFs) are more effective in decreasing renal injury and oxidative stress than deacetylated chitin powder (DAC) in 5/6 nephrectomized rats. An oral administration of low doses of SDACNFs (40mg/kg/day) over a 4 week period resulted in a significant decrease in serum indoxyl sulfate, creatinine and urea nitrogen levels, compared with a similar treatment with DAC or AST-120. The SDACNFs treatment also resulted in an increase in antioxidant potential, compared with that for DAC or AST-120. Immunohistochemical analyses also demonstrated that SDACNFs treated CRF rats showed a decrease in the amount of accumulated 8-OHdG compared with the CRF group. These results suggest that the ingestion of SDCH-NF results in a significant reduction in the levels of pro-oxidants, such as uremic toxins, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation.

  18. Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1.

    PubMed

    Piechowicz, Katarzyna A; Truong, Eric C; Javed, Kashif M; Chaney, Rachelle R; Wu, Johnny Y; Phuan, Puay W; Verkman, Alan S; Anderson, Marc O

    2016-12-01

    Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca(2+) activated Cl(-) channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ∼1 μM for inhibition of TMEM16A chloride conductance.

  19. Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1

    PubMed Central

    Piechowicz, Katarzyna A.; Truong, Eric C.; Javed, Kashif M.; Chaney, Rachelle R.; Wu, Johnny Y.; Phuan, Puay W.; Verkman, Alan S.; Anderson, Marc O.

    2016-01-01

    Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca2+ activated Cl− channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 µM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ~1 µM for inhibition of TMEM16A chloride conductance. PMID:26796863

  20. 3,4,5,6-tetramethylphenanthrene 9,10-oxide: a step on the way to the transition state for nucleophilic ring opening of arene oxides

    SciTech Connect

    Darnow, J.N.; Armstrong, R.N.

    1987-05-01

    Force field calculations (MM2) and studies of the parent hydrocarbons suggest that 3,4,5,6-tetramethylphenanthrene 9,10-oxide (TMPO) should exist as two kinetically stable enantiomers. Stereoelectronic considerations indicate that the axial chirality of each enantiomer should direct nucleophilic attack to the diastereotopic oxirane carbon that most closely approaches the geometry of the transition state. The two enantiomers of TMPO can be synthesized from the chiral hydrocarbons by direct oxidation. The half-life for racemization of TMPO is 30 min at 25/sup 0/C. The two enantiomers are found to be substrates for glutathione (GSH) transferase and epoxide hydrolase. Isozyme 4-4 of GSH transferase which normally catalyzes addition of GSH to oxirane carbons of R absolute configuration, catalyzes addition to the oxirane carbon of S configuration in the M-isomer of TMPO and of R configuration in the P-isomer. Analogous results are obtained with the epoxide hydrolase catalyzed addition of water. The results suggest that TMPO should be an interesting stereochemical probe of both spontaneous and enzyme catalyzed ring opening reactions of arene oxides.