Science.gov

Sample records for 5-6 times higher

  1. 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…

  2. 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;…

  3. Sleep Disorders 6 Times Higher Among Veterans

    MedlinePlus

    ... gov/news/fullstory_159985.html Sleep Disorders 6 Times Higher Among Veterans Post-traumatic stress disorder increases ... 20, 2016 (HealthDay News) -- Sleep disorders are six times more likely among American military veterans than in ...

  4. 11 CFR 5.6 - Fees.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CFR 5.6(a) include, but are not limited to, the following: Advisory Opinion Index Report on Financial... ELECTION COMMISSION ACCESS TO PUBLIC DISCLOSURE DIVISION DOCUMENTS § 5.6 Fees. (a)(1) Fees will be charged... Time/Photocopying Time Clerical: First 1/2 hour is free; remaining time costs $4.50 per each half...

  5. 11 CFR 5.6 - Fees.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CFR 5.6(a) include, but are not limited to, the following: Advisory Opinion Index Report on Financial... ELECTION COMMISSION ACCESS TO PUBLIC DISCLOSURE DIVISION DOCUMENTS § 5.6 Fees. (a)(1) Fees will be charged... Time/Photocopying Time Clerical: First 1/2 hour is free; remaining time costs $4.50 per each half...

  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. Strategies for Hard Times in Higher Education.

    ERIC Educational Resources Information Center

    Desfosses, Louis R.

    1996-01-01

    Planning and management strategies used in the private sector have practical applications for higher education in a period of systemic and organizational stress. Promising strategies include organizational delayering; employee empowerment; boundless thinking, problem-solving teams; accelerated processes; quality management and improvement; and…

  8. 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

  9. 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

  10. 4 CFR 5.6 - Allowances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Allowances. 5.6 Section 5.6 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.6 Allowances. The provisions of chapter 59 of title 5, U.S. Code and the implementing regulations for the Executive Branch apply to Government...

  11. 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....

  12. 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....

  13. 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....

  14. 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....

  15. 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....

  16. 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…

  17. 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…

  18. 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 Election (or…

  19. 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…

  20. 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...

  1. 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... COMMERCIAL AND PRIVATE OPERATIONS § 5.6 Commercial vehicles. (a) The term “Commercial vehicle” as used in... used in connection with any business. (b) The use of government roads within park areas by...

  2. 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... 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...

  3. 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...

  4. 41 CFR 51-5.6 - Shipping.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Shipping. 51-5.6 Section 51-5.6 Public Contracts and Property Management Other Provisions Relating to Public Contracts COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED 5-CONTRACTING REQUIREMENTS §...

  5. 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 investigation…

  6. 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…

  7. 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.

  8. New synthesis of 5,6-benzindole

    SciTech Connect

    Shagalov, L.B.; Ostapchuk, G.M.; Ivanova, T.M.; Suvorov, N.N.

    1987-12-01

    A method has been developed for the synthesis of linear 5,6-benzindole by reduction of N-acetyl-5,6-benzindoxy with NaBH/sub 4/ and subsequent hydrolysis of the N-acetyl group. The PMR spectra were obtained on a Varian H-100 spectrometer in solutions of acetone-d/sub 6/ and chloroform-d/sub 3/ with TMA as internal standard. IR spectra were recorded on a Perkin-Elmer 180 spectrometer in KBr disks or in chloroform solutions in standard cells. TLC was conducted on Silufol UV-254 plates, with chloroform as eluent.

  9. 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... HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION General Provisions § 5.6 Congressional information. Nothing in this part authorizes withholding information from the Congress except when...

  10. 11 CFR 5.6 - Fees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... CFR 5.6(a) include, but are not limited to, the following: Advisory Opinion Index Report on Financial... ID numbers. Requests for more than 20 ID numbers will cost $.05 for each ID number requested. E Index (Parts 1-4)—Candidate Index of Supporting Documents—No charge for requests of 20 or fewer candidate...

  11. 44 CFR 5.6 - Congressional information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Congressional information. 5... HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION General Provisions § 5.6 Congressional information. Nothing in this part authorizes withholding information from the Congress except when...

  12. 11 CFR 5.6 - Fees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CFR 5.6(a) include, but are not limited to, the following: Advisory Opinion Index Report on Financial... ID numbers. Requests for more than 20 ID numbers will cost $.05 for each ID number requested. E Index (Parts 1-4)—Candidate Index of Supporting Documents—No charge for requests of 20 or fewer candidate...

  13. 11 CFR 5.6 - Fees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CFR 5.6(a) include, but are not limited to, the following: Advisory Opinion Index Report on Financial... ID numbers. Requests for more than 20 ID numbers will cost $.05 for each ID number requested. E Index (Parts 1-4)—Candidate Index of Supporting Documents—No charge for requests of 20 or fewer candidate...

  14. 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.

  15. Real-time operating systems at higher control

    SciTech Connect

    Jensen, E.D.

    1995-01-01

    Although virtually all development of real-time operating systems focuses on the lowest of the three traditional control levels, sheet economics demands higher level real-time OSs. Meeting this demand requires a major change in the mindset of the people who have been focusing on the lowest level of control. {open_quotes}These people are trying to deal with an elephant`s tail, but they don`t realize that there is an elephant attached to it.{close_quotes} For more than three decades, the historical real-time mindset, concepts and techniques have been driven by a particular pair of contexts. First is the application context, which can be characterized as {open_quotes}small, simple, centralized, static subsystems for low-level, sampled data, monitoring and first-order control.{close_quotes} Second is the hardware context, characterized by a scarcity of hardware resources due to size, weight, power and cost considerations. Both of these contexts are changing dramatically in ways that {open_quotes}have a significant impact on the concepts and techniques of real-time computing.{close_quotes} Hardware now offers much higher performance and the real-time domain is expanding upward in the application control hierarchy.

  16. 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.

  17. Late-time acceleration in higher dimensional cosmology

    SciTech Connect

    Pahwa, Isha; Choudhury, Debajyoti; Seshadri, T.R. E-mail: debajyoti.choudhury@gmail.com

    2011-09-01

    We investigate late time acceleration of the universe in higher dimensional cosmology. The content in the universe is assumed to exert pressure which is different in the normal and extra dimensions. Cosmologically viable solutions are found to exist for simple forms of the equation of state. The parameters of the model are fixed by comparing the predictions with supernovae data. While observations stipulate that the matter exerts almost vanishing pressure in the normal dimensions, we assume that, in the extra dimensions, the equation of state is of the form P∝ρ{sup 1−γ}. For appropriate choice of parameters, a late time acceleration in the universe occurs with q{sub 0} and z{sub tr} being approximately -0.46 and 0.76 respectively.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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…

  5. California's "Gold Standard" for Higher Education Falls Upon Hard Times

    ERIC Educational Resources Information Center

    Keller, Josh

    2009-01-01

    Few documents in higher education have enjoyed the influence or longevity of the California Master Plan for Higher Education, the 1960 law that transformed the state's public colleges and served as a blueprint for public systems across the country. Even today, almost 50 years after it was written, the master plan retains a mythic status in…

  6. 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…

  7. The fifth spectrum of platinum (Pt V): Analysis of the (5d6 + 5d5 6 s) - 5d5 6 p transition array

    NASA Astrophysics Data System (ADS)

    Azarov, Vladimir I.; Gayasov, Robert R.

    2016-03-01

    The spectrum of platinum was observed in the 300-2100 Å wavelength region. The (5d6 + 5d5 6 s) - 5d5 6 p transition array of four times ionized platinum, Pt V, has been investigated and 1659 spectral lines have been classified in the region of 460-1730 Å. The analysis has led to the determination of the 5d6, 5d5 6 s and 5d5 6 p configurations. Thirty two of 34 theoretically possible 5d6 levels, 45 of 74 possible 5d5 6 s levels and 181 of 214 possible 5d5 6 p levels have been established. The orthogonal operators technique was used to calculate the level structure and transition probabilities. The energy parameters have been determined by the least squares fit to the observed levels. Calculated transition probability and energy values, as well as LS-compositions obtained from the fitted parameters are presented.

  8. Part-Time Students and Their Experience of Higher Education.

    ERIC Educational Resources Information Center

    Bourner, Tom; And Others

    A questionnaire survey sought to determine the characteristics of part-time university students in Great Britain, the reasons why they choose part-time study, the difficulties they encounter, the extent and incidence of non-completion, and to identify examples of "good practice" in the provision and management of part-time degree courses.…

  9. 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,"…

  10. 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…

  11. 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…

  12. Time for Action to Bolster Future of Higher Education

    ERIC Educational Resources Information Center

    Spellings, Margaret

    2007-01-01

    Higher education in America had its origins in New England more than 350 years ago. Since then, America's colleges and universities have been the incubators of great ideas, birthplaces of great inventions, and testing grounds of great individuals. For generations of New Englanders, a college education has provided the opportunity to fully embrace…

  13. 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…

  14. 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)

  15. Numerical Relativity in Higher-Dimensional Space-Times

    NASA Astrophysics Data System (ADS)

    Witek, Helvi

    2013-09-01

    Black holes are among the most exciting phenomena predicted by General Relativity and play a key role in fundamental physics. Many interesting phenomena involve dynamical black hole configurations in the high curvature regime of gravity. In these lecture notes I will summarize the main numerical relativity techniques to explore highly dynamical phenomena, such as black hole collisions, in generic D-dimensional space-times. The present notes are based on my lectures given at the NR/HEP2 spring school at IST/Lisbon (Portugal) from March 11-14, 2013.

  16. 6 CFR 5.6 - Responses to requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 6 Domestic Security 1 2014-01-01 2014-01-01 false Responses to requests. 5.6 Section 5.6 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY DISCLOSURE OF RECORDS AND INFORMATION Freedom of Information Act § 5.6 Responses to requests. (a) Acknowledgements of requests. On receipt of a request, a component ordinarily...

  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. 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.…

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

    PubMed

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

    2013-05-01

    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

  20. 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…

  1. The Benefits of Part-Time Undergraduate Study and UK Higher Education Policy: A Literature Review

    ERIC Educational Resources Information Center

    Bennion, Alice; Scesa, Anna; Williams, Ruth

    2011-01-01

    Part-time study in the UK is significant: nearly 40 per cent of higher education students study part-time. This article reports on a literature review that sought to understand the economic and social benefits of part-time study in the UK. It concludes that there are substantial and wide-ranging benefits from studying part-time. The article also…

  2. 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…

  3. The Legal Rights of Tenured and Part-Time Faculty Members in Higher Education.

    ERIC Educational Resources Information Center

    Corley, Sherie P.

    A review of faculty-related court decisions in the areas of status, compensation, and unit determination points out legal rights of part-time and full-time faculty in higher education. These rights have been tested and defined by many court cases. Litigation has occurred about the difference between part-time and full-time faculty. In regard to…

  4. 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.

  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. Creating Space for Learning: Conceptualizing Women and Higher Education through Space and Time

    ERIC Educational Resources Information Center

    Moss, Dot

    2004-01-01

    This paper highlights the strengths of giving visibility to the concepts of space and time in research related to women's lives and higher education. It is based on research that explores the everyday practice and experience of women higher education students at a community college in the north of England. It focuses on the ways in which space and…

  7. "The Balancing Act"--Irish Part-Time Undergraduate Students in Higher Education

    ERIC Educational Resources Information Center

    Darmody, Merike; Fleming, Bairbre

    2009-01-01

    While the numbers of part-time students has increased in higher education in Ireland, little is known about these students or about how they balance their study and other commitments. Drawing on a larger study on Irish students' experiences in higher education, this article attempts to address this gap in research and reports on Irish part-time…

  8. 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…

  9. 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,…

  10. 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…

  11. 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

  12. Efficient alcoholysis of 5,6-dihydro-1,10-phenanthroline-5,6-epoxide with ytterbium(III) triflate and subsequent enantioselective transesterification with lipases

    PubMed Central

    Schoffers, Elke; Kohler, Lars

    2009-01-01

    New 5,6-dihydro-1,10-phenanthroline derivatives were prepared in high yield via ytterbium(III) triflate-catalyzed alcoholysis of the corresponding epoxide. Enzymatic transesterifications of racemic alkoxy alcohols afforded enantioselective separations with up to 99% ee. The lipase derived from Burkholderia cepacia (PSCI) was the most efficient, with E-values of up to 200. The steric effect of substituents in the 6-position on reaction time and enantioselectivities was assessed. PMID:20160975

  13. Predicting Hyper-Chaotic Time Series Using Adaptive Higher-Order Nonlinear Filter

    NASA Astrophysics Data System (ADS)

    Zhang, Jia-Shu; Xiao, Xian-Ci

    2001-03-01

    A newly proposed method, i.e. the adaptive higher-order nonlinear finite impulse response (HONFIR) filter based on higher-order sparse Volterra series expansions, is introduced to predict hyper-chaotic time series. The effectiveness of using the adaptive HONFIR filter for making one-step and multi-step predictions is tested based on very few data points by computer-generated hyper-chaotic time series including the Mackey-Glass equation and four-dimensional nonlinear dynamical system. A comparison is made with some neural networks for predicting the Mackey-Glass hyper-chaotic time series. Numerical simulation results show that the adaptive HONFIR filter proposed here is a very powerful tool for making prediction of hyper-chaotic time series.

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

    PubMed

    Liu, Xiangjie; Han, Yaozhen

    2014-11-01

    Considering a class of MIMO uncertain nonlinear system, a novel finite time stable control algorithm is proposed based on higher-order sliding mode concept. The higher-order sliding mode control problem of MIMO nonlinear system is firstly transformed into finite time stability problem of multivariable system. Then continuous control law, which can guarantee finite time stabilization of nominal integral chain system, is employed. The second-order sliding mode is used to overcome the system uncertainties. High frequency chattering phenomenon of sliding mode is greatly weakened, and the arbitrarily fast convergence is reached. The finite time stability is proved based on the quadratic form Lyapunov function. Examples concerning the triple integral chain system with uncertainty and the hovercraft trajectory tracking are simulated respectively to verify the effectiveness and the robustness of the proposed algorithm. PMID:25277626

  15. 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.

  16. 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.

  17. "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…

  18. 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 top 200…

  19. 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…

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

    PubMed

    Tran, Martin; Tsarouhas, Vasilios; Kegel, Andreas

    2016-01-01

    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

  1. 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

  2. MultiFacTV: module detection from higher-order time series biological data

    PubMed Central

    2013-01-01

    Background Identifying modules from time series biological data helps us understand biological functionalities of a group of proteins/genes interacting together and how responses of these proteins/genes dynamically change with respect to time. With rapid acquisition of time series biological data from different laboratories or databases, new challenges are posed for the identification task and powerful methods which are able to detect modules with integrative analysis are urgently called for. To accomplish such integrative analysis, we assemble multiple time series biological data into a higher-order form, e.g., a gene × condition × time tensor. It is interesting and useful to develop methods to identify modules from this tensor. Results In this paper, we present MultiFacTV, a new method to find modules from higher-order time series biological data. This method employs a tensor factorization objective function where a time-related total variation regularization term is incorporated. According to factorization results, MultiFacTV extracts modules that are composed of some genes, conditions and time-points. We have performed MultiFacTV on synthetic datasets and the results have shown that MultiFacTV outperforms existing methods EDISA and Metafac. Moreover, we have applied MultiFacTV to Arabidopsis thaliana root(shoot) tissue dataset represented as a gene×condition×time tensor of size 2395 × 9 × 6(3454 × 8 × 6), to Yeast dataset and Homo sapiens dataset represented as tensors of sizes 4425 × 6 × 6 and 2920×14×9 respectively. The results have shown that MultiFacTV indeed identifies some interesting modules in these datasets, which have been validated and explained by Gene Ontology analysis with DAVID or other analysis. Conclusion Experimental results on both synthetic datasets and real datasets show that the proposed MultiFacTV is effective in identifying modules for higher-order time series biological data. It provides, compared to traditional non

  3. 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 description of…

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

    SciTech Connect

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

    1990-08-09

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

  5. Higher-order brick-tetrahedron hybrid method for Maxwell's equations in time domain

    NASA Astrophysics Data System (ADS)

    Winges, Johan; Rylander, Thomas

    2016-09-01

    We present a higher-order brick-tetrahedron hybrid method for Maxwell's equations in time domain. Brick-shaped elements are used for large homogeneous parts of the computational domain, where we exploit mass-lumping and explicit time-stepping. In regions with complex geometry, we use an unstructured mesh of tetrahedrons that share an interface with the brick-shaped elements and, at the interface, tangential continuity of the electric field is imposed in the weak sense by means of Nitsche's method. Implicit time-stepping is used for the tetrahedrons together with the interface. For cavity resonators, the hybrid method reproduces the lowest non-zero eigenvalues with correct multiplicity and, for geometries without field singularities from sharp corners or edges, the numerical eigenvalues converge towards the analytical result with an error that is approximately proportional to h2p, where h is the cell size and p is the polynomial order of the elements. For a rectangular waveguide, a layer of tetrahedrons embedded in a grid of brick-shaped elements yields a low reflection coefficient that scales approximately as h2p. Finally, we demonstrate hybrid time-stepping for a lossless closed cavity resonator, where the time-domain response is computed for 300,000 time steps without any signs of instabilities.

  6. High antiallergic activity of 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone and 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone from eau de cologne mint (Mentha×piperita citrata).

    PubMed

    Sato, Akihiko; Tamura, Hirotoshi

    2015-04-01

    The following compounds with higher antiallergic activities were isolated from eau de cologne mint leaves: 5,6,4'-trihydroxy-7,8-dimethoxyflavone (6), 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone (7), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (8), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone (9), and 5,6-dihydroxy-7,8,4'-trimethoxyflavone (10). The IC50 values of compounds 6-10 against RBL-2H3 cells were 6.7, 2.4, 5.6, 3.0, and 6.1μM. Compounds 7 and 9 (IC50 2.4μM and 3.0μM) had the highest antiallergic activities among the flavonoids previously reported. The amounts of 7, 9, and 10 isolated were fairly high, at 177.7mg/kg, 278.0mg/kg, and 179.7mg/kg in the mint, respectively. LD5 value (index of toxicity) and LD5/IC50 ratio of 7 and 9 indicate that the safety is greater than that of luteolin, a typical antiallergic substance. The extract containing powerful antiallergic flavones, 6-10 with higher hydrophobicity could be selectively separated from the extract containing luteolin and other flavonoid glycosides by partition with dichloromethane and water. Therefore, compounds 7 and 9 in mint, and the dichloromethane extract would be the most potent and preventive resources against type I allergy. PMID:25704366

  7. Wavelet Transform Based Higher Order Statistical Analysis of Wind and Wave Time Histories

    NASA Astrophysics Data System (ADS)

    Habib Huseni, Gulamhusenwala; Balaji, Ramakrishnan

    2016-06-01

    Wind, blowing on the surface of the ocean, imparts the energy to generate the waves. Understanding the wind-wave interactions is essential for an oceanographer. This study involves higher order spectral analyses of wind speeds and significant wave height time histories, extracted from European Centre for Medium-Range Weather Forecast database at an offshore location off Mumbai coast, through continuous wavelet transform. The time histories were divided by the seasons; pre-monsoon, monsoon, post-monsoon and winter and the analysis were carried out to the individual data sets, to assess the effect of various seasons on the wind-wave interactions. The analysis revealed that the frequency coupling of wind speeds and wave heights of various seasons. The details of data, analysing technique and results are presented in this paper.

  8. 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.

  9. 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.

  10. 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

  11. Higher levels of CO2 during late incubation alter the hatch time of chicken embryos.

    PubMed

    Tong, Q; McGonnell, I M; Roulston, N; Bergoug, H; Romanini, C E B; Garain, P; Eterradossi, N; Exadaktylos, V; Bahr, C; Berckmans, D; Demmers, T G M

    2015-01-01

    1. It has been reported that the increasing CO2 tension triggers the embryo to pip the air cell and emerge from the egg. However, the mechanism by which higher CO2 concentrations during the last few days of incubation affect chick physiology and the hatching process is unclear. This study investigated the effect of CO2 concentrations up to 1% during pipping, on the onset and length of the hatch window (HW) and chick quality. 2. Four batches of Ross 308 broiler eggs (600 eggs per batch) were incubated in two small-scale custom-built incubators (Petersime NV). During the final 3 d of incubation, control eggs were exposed to a lower CO2 concentration (0.3%), while the test eggs experienced a higher CO2 concentration programme (peak of 1%). 3. There were no significant differences in blood values, organ weight and body weight. There was also no difference in hatchability between control and test groups. However, a small increase in the chick weight and the percentage of first class chicks was found in the test groups. Furthermore, plasma corticosterone profiles during hatching were altered in embryos exposed to higher CO2; however, they dropped to normal levels at d 21 of incubation. Importantly, the hatching process was delayed and synchronised in the test group, resulting in a narrowed HW which was 2.7 h shorter and 5.3 h later than the control group. 4. These results showed that exposing chicks to 1% CO2 concentration during pipping did not have negative impacts on physiological status of newly hatched chicks. In addition, it may have a significant impact on the physiological mechanisms controlling hatching and have benefits for the health and welfare of chickens by reducing the waiting time after hatching. PMID:25900009

  12. 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.

  13. 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

  14. Automated Determination of P-Wave Arrival Times Using Higher Order Statistics

    NASA Astrophysics Data System (ADS)

    Kueperkoch, L.; Meier, T.; Friederich, W.

    2009-04-01

    Due to the continuously increasing amount of digital, seismological data, automatic localication of seismic events becomes more and more important. The main difficulty is the automatic identification and precise determination of P- and S-wave arrival times. Here we present an algorithm based on higher order statistics for the automated determination of P-onsets of local and regional seismic events. Using the 4th central moment, a characteristic function is calculated, on which the "picker" is applied. Important is the automatic estimation of the quality of the P-onset. In order to get rid off false P-readings, several algorithms are applied to single station as well as to the finishing multy station processing. The robustness and reliability of the automatic has been tested on a very heterogeneous data set of the temporary, regional seismological network EGELADOS, using manual P-readings, which serve as reference picks, as well as by a comparison with the Allen- and the Baer- & Kradolfer-picker. The accuracy and the speed of the presented automatic makes this processing scheme to an option for the implementation into a near-real time processing, e.g. for earthquake early-warning systems.

  15. 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

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

    PubMed

    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

    2016-02-18

    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

  17. 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.

  18. 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;…

  19. 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…

  20. Part-Time Students and Part-Time Study in Higher Education in the UK: Strand 2--A Survey of the Issues Facing Institutions

    ERIC Educational Resources Information Center

    Boorman, Susan; Brown, Nigel; Payne, Philip; Ramsden, Brian

    2006-01-01

    This is the report on part-time study in UK higher education institutions (HEIs) for Universities UK and GuildHE (previously SCOP) from Nigel Brown Associates. It forms Strand 2 of the wider research into part-time higher education commissioned by Universities UK and GuildHE using quantitative data not available from published sources and…

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

    ERIC Educational Resources Information Center

    Orkodashvili, Mariam

    2012-01-01

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

  2. 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…

  3. Troubled Times for American Higher Education: The 1990s and Beyond. SUNY Series, Frontiers in Education.

    ERIC Educational Resources Information Center

    Kerr, Clark; And Others

    This volume looks at the future of American higher education in 13 essays most of which were originally speeches to gatherings around the United States and the globe. The first series of essays in Part I looks at possible "contours" of the future and what choices should be made by higher education to advance the quality of future performance. One…

  4. 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…

  5. Higher Education Enrollments and Student Success in Times of Budget Scarcity: Examining System-Level Impacts in Recessionary Periods

    ERIC Educational Resources Information Center

    Wetstein, Matthew; Hays, Brianna; Nguyen, Alyssa

    2011-01-01

    This study seeks to extend the literature on higher education enrollment patterns during times of recession by examining patterns of enrollment and successful course completion in one of the world's largest higher education systems--the California Community College system. The data are drawn from publicly available data sources on the web. CCC…

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Microbial Dechlorination of 2,3,5,6-Tetrachlorobiphenyl under Anaerobic Conditions in the Absence of Soil or Sediment

    PubMed Central

    Cutter, Leah; Sowers, Kevin R.; May, Harold D.

    1998-01-01

    Bacterial enrichment cultures developed with Baltimore Harbor (BH) sediments were found to reductively dechlorinate 2,3,5,6-tetrachlorobiphenyl (2,3,5,6-CB) when incubated in a minimal estuarine medium containing short-chain fatty acids under anaerobic conditions with and without the addition of sediment. Primary enrichment cultures formed both meta and ortho dechlorination products from 2,3,5,6-CB. The lag time preceding dechlorination decreased from 30 to less than 20 days as the cultures were sequentially transferred into estuarine medium containing dried, sterile BH sediment. In addition, only ortho dechlorination was observed following transfer of the cultures. Sequential transfer into medium without added sediment also resulted in the development of a strict ortho-dechlorinating culture following a lag of more than 100 days. Upon further transfer into the minimal medium without sediment, the lag time decreased to less than 50 days. At this stage all cultures, regardless of the presence of sediment, would produce 2,3,5-CB and 3,5-CB from 2,3,5,6-CB. The strict ortho-dechlorinating activity in the sediment-free cultures has remained stable for more than 1 year through several transfers. These results reveal that the classical microbial enrichment technique using a minimal medium with a single polychlorinated biphenyl (PCB) congener selected for ortho dechlorination of 2,3,5,6-CB. Furthermore, this is the first report of sustained anaerobic PCB dechlorination in the complete absence of soil or sediment. PMID:9687458

  12. Use of Part-Time Faculty in Higher Education: Numbers and Impact. Briefing Papers.

    ERIC Educational Resources Information Center

    Miller, Ross

    Colleges and universities of all kinds rely on part-time faculty to teach students from the freshman year through graduate studies, although they are more likely to teach lower division students. Overall, 43% of postsecondary instructional faculty work part-time, while full-time tenure track positions are held by about 18% of faculty members.…

  13. Classical and quantum-mechanical axioms with the higher time derivative formalism

    NASA Astrophysics Data System (ADS)

    Kamalov, Timur

    2013-06-01

    A Newtonian mechanics model is essentially the model of a point body in an inertial reference frame. How to describe extended bodies in non-inertial (vibration) reference frames with the random initial conditions? One of the most generalized ways of descriptions (known as the higher derivatives formalism) consists in taking into account the infinite number of the higher temporal derivatives of the coordinates in the Lagrange function. Such formalism describing physical objects in the infinite dimensions space does not contradict to the quantum mechanics and infinite dimensions Hilbert space.

  14. Examining a Higher Education Funding Formula in a Time of Shifting Currents: Kentucky's Benchmark Approach

    ERIC Educational Resources Information Center

    Wall, Andrew; Frost, Robert; Smith, Ryan; Keeling, Richard

    2008-01-01

    Although datasets such as the Integrated Postsecondary Data System are available as inputs to higher education funding formulas, these datasets can be unreliable, incomplete, or unresponsive to criteria identified by state education officials. State formulas do not always match the state's economic and human capital goals. This article analyzes…

  15. Retention and Attrition of Students in Higher Education: Challenges in Modern Times to What Works

    ERIC Educational Resources Information Center

    Maher, Marguerite; Macallister, Helen

    2013-01-01

    Retention and attrition rates in higher education have long been a focus of research. This paper presents findings of a single case study, undertaken in a School of Education, which identify important strategies that have led to attrition of five to eight per cent, compared with 18 per cent cross the education sector in Australia (Department of…

  16. 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…

  17. Building a Strong Future for Higher Education: Strategies for Tough Economic Times

    ERIC Educational Resources Information Center

    Higdon, Leo I., Jr.

    2010-01-01

    This is no ordinary recession. And, for leaders in higher education, its impact will resonate long after it has passed. In the years ahead, the author believes that the past thirty years will be viewed as a kind of golden age of academic prosperity that was brought to a crashing end by this recession. Yet, the end of the golden age has also…

  18. Time to Look Anew: Critical Pedagogy and Disciplines within Higher Education

    ERIC Educational Resources Information Center

    McArthur, Jan

    2010-01-01

    This article explores the attitudes of writers within the tradition of critical pedagogy towards disciplines in higher education. With particular focus on Henry Giroux's work, it contrasts his portrayal of disciplines as closed, limiting and elitist with an alternative one of disciplines as complex, permeable and contested spaces. Critical…

  19. 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…

  20. 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…

  1. 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…

  2. Breadth vs. Depth: The Timing of Specialization in Higher Education. NBER Working Paper No. 15943

    ERIC Educational Resources Information Center

    Malamud, Ofer

    2010-01-01

    This paper examines the tradeoff between early and late specialization in the context of higher education. While some educational systems require students to specialize early by choosing a major field of study prior to entering university, others allow students to postpone this choice. I develop a model in which individuals, by taking courses in…

  3. Do Diligent Students Perform Better? Complex Relations between Student and Course Characteristics, Study Time, and Academic Performance in Higher Education

    ERIC Educational Resources Information Center

    Masui, Chris; Broeckmans, Jan; Doumen, Sarah; Groenen, Anne; Molenberghs, Geert

    2014-01-01

    Research has reported equivocal results regarding the relationship between study time investment and academic performance in higher education. In the setting of the active, assignment-based teaching approach at Hasselt University (Belgium), the present study aimed (a) to further clarify the role of study time in academic performance, while taking…

  4. The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.

    PubMed

    Cox, Jason M; Chu, Hong D; Kuethe, Jeffrey T; Gao, Ying-Duo; Scapin, Giovanna; Eiermann, George; He, Huaibing; Li, Xiaohua; Lyons, Kathryn A; Metzger, Joseph; Petrov, Aleksandr; Wu, Joseph K; Xu, Shiyao; Sinha-Roy, Ranabir; Weber, Ann E; Biftu, Tesfaye

    2016-06-01

    Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans. PMID:27106708

  5. 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.

  6. 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.

  7. 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. PMID:20382673

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

    PubMed Central

    Liu, Lin; De, Subhajyoti; Michor, Franziska

    2013-01-01

    Single nucleotide substitutions (SNS) are a defining characteristic of cancer genomes. Many SNS in cancer genomes arise due to 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 SNS 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 SNS in normal and cancer genomes. PMID:23422670

  9. 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…

  10. 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…

  11. Widening Participation, Social Justice and Injustice: Part-Time Students in Higher Education in England

    ERIC Educational Resources Information Center

    Callender, Claire

    2011-01-01

    This article critically assesses the nature and scope of current financial support for part-time undergraduates in England, highlighting its importance for widening participation. It considers the limitations of these financial arrangements, why they are in need of reform, and some of the consequences of their inadequacies. The paper argues that…

  12. Using higher organisms in biological early warning systems for real-time toxicity detection.

    PubMed

    van der Schalie, W H; Shedd, T R; Knechtges, P L; Widder, M W

    2001-09-01

    Many biological early warning systems (BEWS) have been developed in recent years that evaluate the physiological and behavioral responses of whole organisms to water quality. Using a fish ventilatory monitoring system developed at the US Army Centre for Environmental Health Research as an example, we illustrate the operation of a BEWS at a groundwater treatment facility. During a recent 12-month period, the fish ventilatory system was operational for 99% of the time that the treatment facility was on-line. Effluent-exposed fish responded as a group about 2.8% of the time. While some events were due to equipment problems or non-toxic water quality variations, the fish system did indicate effluent anomalies that were subsequently identified and corrected. The fish monitoring BEWS increased treatment facility engineers' awareness of effluent quality and provided an extra measure of assurance to regulators and the public. Many operational and practical considerations for whole organism BEWS are similar to those for cell- or tissue-based biosensors. An effective biomonitoring system may need to integrate the responses of several biological and chemical sensors to achieve desired operational goals. Future development of an 'electronic canary', analogous to the original canary in the coal mine, could draw upon advances in signal processing and communication to establish a network of sensors in a watershed and to provide useful real-time information on water quality. PMID:11544040

  13. 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…

  14. Identification of Impact Location in a Plate Based on Elastodynamics and Higher Order Time Frequency Method

    NASA Astrophysics Data System (ADS)

    Lee, S. K.; Kim, S. J.

    In a nuclear power plant, impact force due to loose part is related to the structural damage in the plant. In general, the steam generator of the nuclear power plant is structured by thick plate. The paper presents a novel approach to locate an impact load in a thick plate. The approach is based on the analysis of the acoustic waveforms measured by a sensor array located on the plate surface. For accurate estimation of the location of the impact source, the time differences in the arrival times of the waves at the sensors and their propagation velocities are determined. The dispersion curves for multi modes of Lamb wave are calculated by using exact plate theory and SDPT. It is difficult to measure directly the group velocity for Lamb mode of acoustic waveform in the thick plate because they are dispersive wave. However, most of the energy in the wave is carried by the flexural waves (A0 mode), the group velocity of this mode is extracted using the CHOTF technique for estimating the impact source location. The estimates are shown to be in excellent agreement with the actual locations and it is applied to the damage analysis due to the loose part in a nuclear power plant.

  15. 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.…

  16. 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…

  17. 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…

  18. 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…

  19. 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.

  20. 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

  1. Field orientation effects during 5. 6-GHz radiofrequency irradiation of rats

    SciTech Connect

    Frei, M.R.; Jauchem, J.R.; Price, D.L.; Padilla, J.M. )

    1990-12-01

    Ketamine-anesthetized Sprague-Dawley rats were exposed in E and H orientations (long axis parallel to electric and magnetic fields, respectively) to far-field 5.6-GHz continuous-wave radio-frequency radiation (RFR). Power densities were used that resulted in equivalent whole-body average specific absorption rates of 14 W/kg in both orientations (90 mW/cm2 for E and 66 mW/cm2 for H). Irradiation was conducted to increase colonic temperature by 1 degree C (from 38.5 to 39.5 degrees C). During experimentation, arterial blood pressure and respiratory rate and colonic, tympanic, left and right subcutaneous (sides toward and away from RFR source), and tail temperatures were continuously recorded. Results showed no significant difference in the times required to cause a 1 degree C increase or to recover to the initial temperature when irradiation was stopped. Significant differences between E- and H-orientation exposure were seen in the patterns of localized heating. The tail and left subcutaneous temperature increases were significantly greater during E-orientation exposure, the tympanic site showed no difference, and the right subcutaneous temperature increase was significantly greater during H-orientation exposure. Under both exposure conditions, heart rate and mean arterial blood pressure significantly increased during irradiation; however, there were no significant differences between E and H orientation responses. These findings at 5.6 GHz are in contrast to the significant cardiovascular response differences between E- and H-orientation exposure noted during a previous study of irradiation at 2.45 GHz.

  2. 43 CFR 3585.5-6 - Publication and posting of notice.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Publication and posting of notice. 3585.5-6 Section 3585.5-6 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) SPECIAL LEASING AREAS...

  3. 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…

  4. 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...

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

    PubMed

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

    2014-01-01

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

  6. The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties.

    PubMed

    Kovalevskaya, Nadezda V; Bokhovchuk, Fedir M; Vuister, Geerten W

    2012-06-01

    The epithelial Ca(2+) channels TRPV5/6 (transient receptor potential vanilloid 5/6) are thoroughly regulated in order to fine-tune the amount of Ca(2+) reabsorption. Calmodulin has been shown to be involved into calcium-dependent inactivation of TRPV5/6 channels by binding directly to the distal C-terminal fragment of the channels (de Groot et al. in Mol Cell Biol 31:2845-2853, 12). Here, we investigate this binding in detail and find significant differences between TRPV5 and TRPV6. We also identify and characterize in vitro four other CaM binding fragments of TRPV5/6, which likely are also involved in TRPV5/6 channel regulation. The five CaM binding sites display diversity in binding modes, binding stoichiometries and binding affinities, which may fine-tune the response of the channels to varying Ca(2+)-concentrations. PMID:22354706

  7. Phase transitions between lower and higher level management learning in times of crisis: an experimental study based on synergetics.

    PubMed

    Liening, Andreas; Strunk, Guido; Mittelstadt, Ewald

    2013-10-01

    Much has been written about the differences between single- and double-loop learning, or more general between lower level and higher level learning. Especially in times of a fundamental crisis, a transition between lower and higher level learning would be an appropriate reaction to a challenge coming entirely out of the dark. However, so far there is no quantitative method to monitor such a transition. Therefore we introduce theory and methods of synergetics and present results from an experimental study based on the simulation of a crisis within a business simulation game. Hypothesized critical fluctuations - as a marker for so-called phase transitions - have been assessed with permutation entropy. Results show evidence for a phase transition during the crisis, which can be interpreted as a transition between lower and higher level learning. PMID:24011119

  8. Continuous higher-order sliding mode control with time-varying gain for a class of uncertain nonlinear systems.

    PubMed

    Han, Yaozhen; Liu, Xiangjie

    2016-05-01

    This paper presents a continuous higher-order sliding mode (HOSM) control scheme with time-varying gain for a class of uncertain nonlinear systems. The proposed controller is derived from the concept of geometric homogeneity and super-twisting algorithm, and includes two parts, the first part of which achieves smooth finite time stabilization of pure integrator chains. The second part conquers the twice differentiable uncertainty and realizes system robustness by employing super-twisting algorithm. Particularly, time-varying switching control gain is constructed to reduce the switching control action magnitude to the minimum possible value while keeping the property of finite time convergence. Examples concerning the perturbed triple integrator chains and excitation control for single-machine infinite bus power system are simulated respectively to demonstrate the effectiveness and applicability of the proposed approach. PMID:26920085

  9. Hydrogen peroxide generation associated with the oxidations of the eumelanin precursors 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid.

    PubMed

    Nappi, A J; Vass, E

    1996-10-01

    The ability of iron chelates to promote hydroxyl radical (.OH) formation from hydrogen peroxide (H2O2) via Fenton chemistry was exploited to detect H2O2 produced during the oxidations of the eumelanin precursors 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). H2O2 generation during the autooxidations of DHI and DHICA was confirmed on the basis of the electrochemical detection of three hydroxylation products of salicylate [2,3 and 2,5-dihydroxybenzoic acid (DHBA) and catechol], which was used as an .OH indicator. The oxidations of both 5,6-dihydroxyindoles were augmented by tyrosinase and peroxidase without the addition of H2O2. The partial inhibitions by catalase of the auto-oxidations and tyrosinase- and peroxidase-mediated oxidations of DHI and DHICA provide additional evidence of an endogenous origin of H2O2 during the final stages of eumelanogenesis. The mechanism proposed for the formation of H2O2 involves the semiquinones of DHI and DHICA in the univalent transfer of electrons to molecular oxygen. The observations described in this study support previous reports suggesting that factors modulating the levels of H2O2 in melanocytes and melanoma cells play critical roles in directing the course of melanogenesis and influencing the potential cytotoxicity of the biosynthetic pathways. PMID:8908594

  10. NLRP3 deletion protects against renal fibrosis and attenuates mitochondrial abnormality in mouse with 5/6 nephrectomy.

    PubMed

    Gong, Wei; Mao, Song; Yu, Jing; Song, Jiayu; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

    2016-05-15

    Progressive fibrosis in chronic kidney disease (CKD) is the well-recognized cause leading to the progressive loss of renal function. Emerging evidence indicated a pathogenic role of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in mediating kidney injury. However, the role of NLRP3 in the remnant kidney disease model is still undefined. The present study was undertaken to evaluate the function of NLRP3 in modulating renal fibrosis in a CKD model of 5/6 nephrectomy (5/6 Nx) and the potential involvement of mitochondrial dysfunction in the pathogenesis. Employing NLRP3(+/+) and NLRP3(-/-) mice with or without 5/6 Nx, we examined renal fibrotic response and mitochondrial function. Strikingly, tubulointerstitial fibrosis was remarkably attenuated in NLRP3(-/-) mice as evidenced by the blockade of extracellular matrix deposition. Meanwhile, renal tubular cells in NLRP3(-/-) mice maintained better mitochondrial morphology and higher mitochondrial DNA copy number, indicating an amelioration of mitochondrial abnormality. Moreover, NLRP3 deletion also blunted the severity of proteinuria and CKD-related hypertension. To further evaluate the direct role of NLRP3 in triggering fibrogenesis, mouse proximal tubular cells (PTCs) were subjected to transforming growth factor β1 (TGF-β1), and the cellular phenotypic changes were detected. As expected, TGF-β1-induced alterations of PTC phenotype were abolished by NLRP3 small interfering RNA, in line with a protection of mitochondrial function. Taken together, NLRP3 deletion protected against renal fibrosis in the 5/6 Nx disease model, possibly via inhibiting mitochondrial dysfunction. PMID:26887832

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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…

  17. Higher-order time-symmetry-breaking phase transition due to meeting of an exceptional point and a Fano resonance

    NASA Astrophysics Data System (ADS)

    Tanaka, Satoshi; Garmon, Savannah; Kanki, Kazuki; Petrosky, Tomio

    2016-08-01

    We have theoretically investigated the time-symmetry-breaking phase-transition process for two discrete states coupled with a one-dimensional continuum by solving the nonlinear eigenvalue problem for the effective Hamiltonian associated with the discrete spectrum. We obtain the effective Hamiltonian with use of the Feshbach-Brillouin-Wigner projection method. Strong energy dependence of the self-energy appearing in the effective Hamiltonian plays a key role in the time-symmetry-breaking phase transition: As a result of competition in the decay process between the Van Hove singularity and the Fano resonance, the phase transition becomes a higher-order transition when both the two discrete states are located near the continuum threshold.

  18. Higher Level Phylogeny and the First Divergence Time Estimation of Heteroptera (Insecta: Hemiptera) Based on Multiple Genes

    PubMed Central

    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. PMID:22384163

  19. 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. PMID:22384163

  20. The Relationship of Higher Education to Substance Use Trajectories: Variations as a Function of Timing of Enrollment

    PubMed Central

    THOMPSON, KARA; HOMEL, JACQUELINE; LEADBEATER, BONNIE

    2016-01-01

    Objective This study examined the association between time to enrollment into postsecondary education and trajectories of heavy episodic drinking (HED) and marijuana use using a prospective longitudinal study. Method Participants included 391 postsecondary students (55% female) drawn from the Victoria Healthy Youth Survey, a five-wave, multi-cohort sample interviewed biennially between 2003 and 2011. Using piecewise latent growth modeling, we compared changes in the trajectories of HED and marijuana use before and after postsecondary enrollment across three groups of young adults: (a) direct entrants (enrolled directly out of high school), (b) gap entrants (took a year off), and (c) delayed entrants (took longer than a year off). Results Heavy drinking increased after enrollment for direct entrants and gap entrants and decreased for delayed entrants. Marijuana use increased after enrollment for direct entrants, and decreased for gap entrants and delayed entrants. Yet, overall levels of marijuana use were significantly higher among the gap and delay entrants over time compared with direct entrants. Group differences in heavy drinking appeared to reflect age-related changes in drinking patterns. However, differences in marijuana use may reflect pre-existing inequities in access to higher education across groups. Conclusions The association between postsecondary education and increased substance use may be limited to students who enroll at a postsecondary institution directly out of high school. However, students who delay enrollment have higher levels of substance use before enrollment, as well as lower high school grades and socioeconomic status compared with direct entrants, and may be particularly vulnerable to long-term substance use problems and degree noncompletion. PMID:25486398

  1. Lower theta inter-trial phase coherence during performance monitoring is related to higher reaction time variability: a lifespan study.

    PubMed

    Papenberg, Goran; Hämmerer, Dorothea; Müller, Viktor; Lindenberger, Ulman; Li, Shu-Chen

    2013-12-01

    Trial-to-trial reaction time (RT) variability is consistently higher in children and older adults than in younger adults. Converging evidence also indicates that higher RT variability is (a) associated with lower behavioral performance on complex cognitive tasks, (b) distinguishes patients with neurological deficits from healthy individuals, and also (c) predicts longitudinal cognitive decline in older adults. However, so far the processes underlying increased RT variability are poorly understood. Previous evidence suggests that control signals in the medial frontal cortex (MFC) are reflected in theta band activity and may implicate the coordination of distinct brain areas during performance monitoring. We hypothesized that greater trial-to-trial variability in theta power during performance monitoring may be associated with greater behavioral variability in response latencies. We analyzed event-related theta oscillations assessed during a cued-Go/NoGo task in a lifespan sample covering the age range from middle childhood to old age. Our results show that theta inter-trial coherence during NoGo trials increases from childhood to early adulthood, and decreases from early adulthood to old age. Moreover, in all age groups, individuals with higher variability in medial frontal stimulus-locked theta oscillations showed higher trial-to-trial RT variability behaviorally. Importantly, this effect was strongest at high performance monitoring demands and independent of motor response execution as well as theta power. Taken together, our findings reveal that lower theta inter-trial coherence is related to greater behavioral variability within and across age groups. These results hint at the possibility that more variable MFC control may be associated with greater performance fluctuations. PMID:23876249

  2. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication.

    PubMed

    Murphy, Christopher M; Xu, Yanping; Li, Feng; Nio, Kouki; Reszka-Blanco, Natalia; Li, Xiaodong; Wu, Yaxu; Yu, Yanbao; Xiong, Yue; Su, Lishan

    2016-09-13

    The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression. PMID:27626656

  3. 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

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

    PubMed

    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

  5. Two 6-substituted 5,6-dihydro-alpha-pyrones from Ravensara anisata.

    PubMed

    Andrianaivoravelona, J O; Sahpaz, S; Terreaux, C; Hostettmann, K; Stoeckli-Evans, H; Rasolondramanitra, J

    1999-09-01

    The leaves and bark dichloromethane extracts of Ravensara anisata showed antifungal activity against the yeast Candida albicans and the phytopathogenic fungus Cladosporium cucumerinum in bioautographic TLC assays. Activity-guided fractionation afforded two new alpha-pyrones: 6R*-(4R*-acetoxy-2S*-hydroxy- 8-phenyloctyl)-5,6-dihydro-2-H-pyran-2-one and 6R*-(2S*-acetoxy-4R*- hydroxy-8-phenyloctyl)-5,6-dihydro-2-H-pyran-2-one. Their structures have been established by NMR spectroscopy, chemical methods and X-ray crystallographic analysis. The antifungal activity against C. albicans and C. cucumerinum was determined for both compounds. PMID:10513401

  6. Quantum reaction rate from higher derivatives of the thermal flux-flux autocorrelation function at time zero.

    PubMed

    Ceotto, Michele; Yang, Sandy; Miller, William H

    2005-01-22

    A quantum theory of thermal reaction rates is presented which may be viewed as an extension of the recently developed "quantum instanton" (QI) model [W. H. Miller, Y. Zhao, M. Ceotto, and S. Yang, J. Chem. Phys. 119, 1329 (2003)]. It is based on using higher derivatives of the flux-flux autocorrelation function C(t) (as given by Miller, Schwartz, and Tromp) at t=0 to construct a short time approximation for C(t). Tests of this theory on 1d and collinear reactions, both symmetric and asymmetric, show it to be more accurate than the original QI model, giving rate constants to approximately 5% for a wide range of temperature. PMID:15740237

  7. Quantum reaction rate from higher derivatives of the thermal flux-flux autocorrelation function at time zero

    NASA Astrophysics Data System (ADS)

    Ceotto, Michele; Yang, Sandy; Miller, William H.

    2005-01-01

    A quantum theory of thermal reaction rates is presented which may be viewed as an extension of the recently developed "quantum instanton" (QI) model [W. H. Miller, Y. Zhao, M. Ceotto, and S. Yang, J. Chem. Phys. 119, 1329 (2003)]. It is based on using higher derivatives of the flux-flux autocorrelation function C(t) (as given by Miller, Schwartz, and Tromp) at t=0 to construct a short time approximation for C(t). Tests of this theory on 1d and collinear reactions, both symmetric and asymmetric, show it to be more accurate than the original QI model, giving rate constants to ˜5% for a wide range of temperature.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  10. 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.

  11. 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)

  12. 2,2\\',3,3\\',4,4\\',5,5\\',6,6\\'-Decabromodiphenyl ether (BDE-209)

    Integrated Risk Information System (IRIS)

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

  13. 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...

  14. Pyrogen fever in rabbits pretreated with p-chlorophenylalanine or 5, 6-dihydroxytryptamine.

    PubMed

    Carruba, M O; Bächtold, H P

    1976-06-15

    The hyperthermic effect of a bacterial pyrogen has been studied in rabbits pretreated or not with p-chlorophenylalanine or 5, 6-dihydroxytryptamine. The results obtained indicate that a selective reduction of cerebral 5-hydroxytryptamine levels by these drugs do not significantly affect pyrogen hypertermia. PMID:133031

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

    PubMed

    Galve, Iñaki; Puig de la Bellacasa, Raimon; Sánchez-García, David; Batllori, Xavier; Teixidó, Jordi; Borrell, José I

    2012-11-01

    A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine. PMID:23054532

  2. Automated determination of P-phase arrival times at regional and local distances using higher order statistics

    NASA Astrophysics Data System (ADS)

    Küperkoch, L.; Meier, T.; Lee, J.; Friederich, W.; Working Group, EGELADOS

    2010-05-01

    We present an algorithm for automatic P-phase arrival time determination for local and regional seismic events based on higher order statistics (HOS). Using skewness or kurtosis a characteristic function is determined to which a new iterative picking algorithm is applied. For P-phase identification we apply the Akaike Information Criterion to the characteristic function, while for a precise determination of the P-phase arrival time a pragmatic picking algorithm is applied to a recalculated characteristic function. In addition, an automatic quality estimate is obtained, based on the slope and the signal-to-noise ratio, both calculated from the characteristic function. To get rid of erroneous picks, a Jackknife procedure and an envelope function analysis is used. The algorithm is applied to a large data set with very heterogeneous qualities of P-onsets acquired by a temporary, regional seismic network of the EGELADOS-project in the southern Aegean. The reliability and robustness of the proposed algorithm is tested by comparing more than 3000 manually derived P readings, serving as reference picks, with the corresponding automatically estimated P-wave arrival times. We find an average deviation from the reference picks of 0.26 +/- 0.64s when using kurtosis and 0.38 +/- 0.75s when using skewness. If automatically as excellent classified picks are considered only, the average difference from the reference picks is 0.07 +/- 0.31s and 0.07 +/- 0.41s, respectively. However, substantially more P-arrival times are determined when using kurtosis, indicating that the characteristic function derived from kurtosis estimation is to be preferred. Since the characteristic function is calculated recursively, the algorithm is very fast and hence suited for earthquake early warning purposes. Furthermore, a comparative study with automatically derived P-readings using Allen's and Baer & Kradolfer's picking algorithms applied to the same data set demonstrates better quantitative and

  3. Rhubarb Enema Attenuates Renal Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Alleviating Indoxyl Sulfate Overload

    PubMed Central

    Lu, Fuhua; Liu, Xusheng; Zou, Chuan

    2015-01-01

    Aim To investigate the effects of rhubarb enema treatment using a 5/6 nephrectomized rat model and study its mechanisms. Methods Twenty-eight Sprague Dawley rats were divided into three groups: sham operation group (n = 8), 5/6 nephrectomized (5/6Nx) (n = 10), and 5/6Nx with rhubarb enema treatment (n = 10). The rhubarb enema was continuous for 1.0 month. Serum creatinine, serum indoxyl sulfate (IS) level, renal pathology, tubulointerstitial fibrosis, and renal oxidative stress were assessed. Results 5/6Nx rats showed increasing levels of serum creatinine and severe pathological lesions. Their serum creatinine levels obviously decreased after rhubarb enema treatment (P < 0.05 vs 5/6Nx group). The administration of rhubarb enema attenuated the histopathological changes in 5/6Nx rats. In addition, 5/6Nx rats showed an enhanced extent of tubulointerstitial fibrosis compared with sham rats, and administration of rhubarb enema to 5/6Nx rats ameliorated tubulointerstitial fibrosis. 5/6Nx rats showed increased serum levels of IS, renal oxidative stress, and NF-κB compared with sham rats, whereas administration of rhubarb enema to 5/6Nx rats decreased serum levels of IS, renal oxidative stress, and NF-κB levels. Conclusion Rhubarb enema treatment ameliorates tubulointerstitial fibrosis in the kidneys of 5/6Nx rats, most likely by alleviating IS overload and reducing kidney oxidative stress and inflammatory injury. PMID:26671452

  4. 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.

  5. E. coli QueD is a 6-carboxy-5,6,7,8-tetrahydropterin synthase†

    PubMed Central

    McCarty, Reid M.; Somogyi, Árpád; Bandarian, Vahe

    2009-01-01

    To elucidate the early steps required during biosynthesis of a broad class of 7-deazapurine containing natural products, we have studied the reaction catalyzed by Escherichia coli QueD, a 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase (PTPS) homolog possibly involved in queuosine biosynthesis. While mammalian PTPS homologs convert 7,8-dihydroneopterin triphosphate (H2NTP) to 6-pyruvoyltetrahydropterin (PPH4) in biopterin biosynthesis, E. coli QueD catalyzes the conversion of H2NTP to 6-carboxy-5,6,7,8-tetrahydropterin (CPH4). E. coli QueD can also convert PPH4 and sepiapterin to CPH4, allowing a mechanism to be proposed. PMID:19231875

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

    NASA Astrophysics Data System (ADS)

    Li, Xiyang; Fan, Pingzhi; Wu, Dianhua

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

  7. Dihydro-5,6-dehydrokavain (DDK) from Alpinia zerumbet: Its Isolation, Synthesis, and Characterization.

    PubMed

    Xuan, Tran Dang; Teschke, Rolf

    2015-01-01

    Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its α-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double-bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6. DDK is easily identified and quantified by HPLC and GC. DDK contents in fresh leaves, stems and rhizomes range from 80 to 410 mg/g, requiring solvent extraction procedures to ensure high DDK yield. This is best achieved by hexane extraction from fresh rhizomes that were previously boiled in water, allowing DDK yields of up to 424 mg/g. Successful synthesis of DDK can be achieved by asymmetric pathways, whereas its simple chemical structure facilitates the synthesis of DDK derivatives by HCl hydrolysis. Thus, all synthesized products may be used for various commercial purposes, including the potential development of promising antiobesity pharmaceutical drugs, preparation of specific and safe dietary supplements, and use as effective natural herbicides or fungicides. PMID:26370954

  8. 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

  9. Cytokeratin 5/6 and P63 immunophenotype of thyroid lymphoepithelial complexes.

    PubMed

    Handra-Luca, Adriana; Dragoescu, Ema

    2016-08-01

    Thyroid lymphoepithelial complexes (LECos) are rare, being reported in lymphoma, Graves-Basedow disease, Hashimoto thyroiditis, pericarcinomatous thyroid or in the context of branchial cleft-like cysts. Here we report immunohistochemical expression of cytokeratin 5/6, P63 and TTF1 in 6 cases of thyroid LECos. Two cases had carbimazole treatment for hyperthyroidia and Graves disease. Anti-thyroglobulin, -thyroperoxidase or -TSH antibodies were detected in 4 cases. NSAID or poviodone iodine allergy were present in 2 cases. The treatment consisted in total thyroidectomy or lobectomy. Microscopy showed nodular goiter and focal lymphocytic thyroiditis. Basaloid LECos were seen in all thyroids while squamoid LECos in 2. Associated lesions were papillary thyroid microcarcinoma (2 cases), solid cell nest, thyroglosal duct remnant, lymphoepithelial cyst and thymus-parathyroid unit (one case each). Cytokeratin 5/6 was expressed in both squamoid and basaloid LECos along with P63. TTF1 expression was faint or absent. In conclusion LECos may occur in the context of autoimmune thyroiditis or of a specific immune susceptibility background. The expression of CK5/6 and of P63 suggests a squamous differentiation including in the basaloid LECos. The etiologic relevance of these immunostainings remains limited although rather suggestive of a metaplastic process than of migration-abnormalities. PMID:27130144

  10. A case of T2 radiculopathy after anterior C5-6 fusion.

    PubMed

    Takenaka, Tomofumi; Ohnishi, Yu-Ichiro; Oshino, Satoru

    2016-01-01

    Thoracic radiculopathy is a rare entity. Symptomatic adjacent-segment disease after anterior cervical fusion occurs commonly in the lower cervical spine segment. We describe the clinical presentation and treatment of T2 radiculopathy after C5-6 anterior fusion. A 60-year-old man presented with the right axillary pain for 3 months. He had undergone C5-6 anterior fusion for cervical spondylosis 5 years prior. Computed tomography (CT) and magnetic resonance images showed T2-3 degenerative disease. C5-6 anterior fusion exacerbated the T2-3 segment involved in the patient's scoliotic deformity. After 2 months of conservative treatment, we decompressed the T2 foramen via T2-3 hemilaminectomy and partial facet resection. After the surgery, his symptoms disappeared. T2 radiculopathy is rare but should be considered in the differential diagnosis of chest pain. Surgeons should pay attention not only to adjacent-segment disease but also to segmental degeneration at the apex of a scoliotic deformity after cervical anterior fusion. PMID:27197614

  11. 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

  12. The Campus in Hard Times. New York's Higher Education Crisis. How It Happened. How It Can Be Resolved.

    ERIC Educational Resources Information Center

    Paley, Henry D.

    How did the New York State system of colleges and universities arrive at the brink of fiscal disaster? What is a possible new perception of higher education financing for New York? The radical shift in enrollment from independent to government-sponsored campuses, and the steep escalation in tax-levy burden for higher education resulted in the New…

  13. 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…

  14. Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates.

    PubMed

    Bonner, Jaclyn N; Choi, Koyi; Xue, Xiaoyu; Torres, Nikko P; Szakal, Barnabas; Wei, Lei; Wan, Bingbing; Arter, Meret; Matos, Joao; Sung, Patrick; Brown, Grant W; Branzei, Dana; Zhao, Xiaolan

    2016-07-12

    Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates. PMID:27373152

  15. 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. PMID:26911850

  16. Linear polarization variations modulo 5.6 days in HDE 226868

    NASA Technical Reports Server (NTRS)

    Nolt, I. G.; Kemp, J. C.; Rudy, R. J.; Southwick, R. G.; Radostitz, J. V.; Caroff, L. J.

    1975-01-01

    Results are reported for observations of variations in the linear polarization in HDE 226868 (the optical counterpart of Cyg X-1) made with a photoelastic polarimeter and a U-filter. The UV linear-polarization variations, as folded on the 5.6-day orbital period, are found to have amplitudes of 0.25% and position-angle changes of 2.7 deg. These results are shown to be consistent with the geometry and phasing required by the model of the binary system.

  17. 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.

  18. Mineral bone disorder in chronic kidney disease: head-to-head comparison of the 5/6 nephrectomy and adenine models

    PubMed Central

    2014-01-01

    Background Experimental models are important to the understanding of the pathophysiology of, as well as the effects of therapy on, certain diseases. In the case of chronic kidney disease-mineral bone disorder, there are currently two models that are used in evaluating the disease: 5/6 nephrectomy (Nx) and adenine-induced renal failure (AIRF). However, the two models have never been compared in studies using animals maintained under similar conditions. Therefore, we compared these two models, focusing on the biochemical, bone histomorphometry, and vascular calcification aspects. Methods Wistar rats, initially fed identical diets, were divided into two groups: those undergoing 5/6 Nx (5/6Nx group) and those that were switched to an adenine-enriched diet (AIRF group). After 9 weeks, animals were sacrificed, and we conducted biochemical and bone histomorphometry analyses, as well as assessing vascular calcification. Results At sacrifice, the mean body weight was higher in the 5/6Nx group than in the AIRF group, as was the mean blood pressure. No differences were seen regarding serum phosphate, ionized calcium, intact parathyroid hormone (PTH), or fibroblast growth factor 23 (FGF23). However, creatinine clearance was lower and fractional excretion of phosphate (FeP) was higher in the AIRF group rats, which also had a more severe form of high-turnover bone disease. Vascular calcification, as evaluated through von Kossa staining, was not observed in any of the animals. Conclusions Overt vascular calcification was not seen in either model as applied in this study. Under similar conditions of diet and housing, the AIRF model produces a more severe form of bone disease than does 5/6 Nx. This should be taken into account when the choice is made between these models for use in preclinical studies. PMID:24885705

  19. 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

  20. MnTBAP Therapy Attenuates Renal Fibrosis in Mice with 5/6 Nephrectomy

    PubMed Central

    Yu, Jing; Mao, Song; Zhang, Yue; Gong, Wei; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

    2016-01-01

    Renal fibrosis is a common pathological feature of all kinds of chronic kidney diseases (CKDs) with uncertain mechanisms. Accumulating evidence demonstrated an important role of oxidative stress in the pathogenesis of CKD. Here we hypothesized that MnTBAP (manganese (III) tetrakis (4-benzoic acid)porphyrin chloride), a cell-permeable mimic of superoxide dismutase (SOD), may protect against the fibrotic response in CKD by antagonizing oxidative stress. To verify this hypothesis, we performed experiments in tubular epithelial cells and mice with 5/6 nephrectomy (Nx). In mouse tubular epithelial cells, TGF-β1 induced a significant transition to fibrotic phenotype in line with a remarkable mitochondrial dysfunction, which was markedly improved by MnTBAP (1.14 μM) pretreatment. In remnant kidneys of 5/6 Nx mice, tubulointerstitial fibrosis occurred in parallel with mitochondrial abnormality in renal tubular cells. Administration of MnTBAP significantly attenuated the deposition of extracellular matrix as evidenced by the blocked expressions of fibronectin, collagen I, and collagen III. Masson staining also displayed an ameliorated accumulation of collagenous matrix in MnTBAP-treated mice. Moreover, MnTBAP also significantly improved the severity of proteinuria without altering CKD-related hypertension. Collectively, MnTBAP therapy served as a promising strategy in preventing renal fibrosis in CKDs possibly via antagonizing mitochondrial-derived oxidative stress and subsequent protection of mitochondrial function. PMID:26989454

  1. Excision repair of 5,6-dihydroxydihydrothymine from the DNA of Micrococcus radiodurans

    SciTech Connect

    Targovnik, H.S.; Hariharan, P.V.

    1980-08-01

    One of the major ionizing radiation products, 5,6-dihydroxydihydrothymine (thymine glycol), was measured in the DNA of Micrococcus radiodurans following exposure of cells to 6.8-MeV electrons or 254-nm ultraviolet light. Removal of 5,6-dihydroxydihydrothymine was measured in both an ionizing radiation-sensitive strain (262) and a highly radioresistant strain (the wild type W/sup +/) of Micrococcus radiodurans. Within 30 min of incubation (33/sup 0/C) following exposure to ultraviolet light (2400 J/m/sup 2/) approximately 60% of the thymine glycols were excised, whereas in the case of ionizing radiation (250 krad) only 35% were removed from the cellular DNA of the wild-type strain. In contrast less than 50% of the thymine glycols were excised from the sensitive strain. The amount of DNA degradation induced by radiation was less than 10% in both strains. The results suggest a possible correlation between reduced excision repair of base damage and increased radiation sensitivity.

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

    PubMed

    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; Orange, Jordan S; 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; van Haaften, Gijs

    2016-08-01

    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

  3. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6

    PubMed Central

    Ahn, Victoria E.; Chu, Matthew Ling-Hon; Choi, Hee-Jung; Tran, Denise; Abo, Arie; Weis, William I.

    2011-01-01

    Summary LDL receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt growth factors, and also bind Dkk proteins, secreted inhibitors of Wnt signaling. The LRP5/6 ectodomain contains four β-propeller/EGF-like domain repeats. The first two repeats (LRP6(1-2)) bind to several Wnt variants, whereas LRP6(3-4) binds other Wnts. We present the crystal structure of the Dkk1 C-terminal domain bound to LRP6(3-4), and show that the Dkk1 N-terminal domain binds to LRP6(1-2), demonstrating that a single Dkk1 molecule can bind to both portions of the LRP6 ectodomain and thereby inhibit different Wnts. Small-angle x-ray scattering analysis of LRP6(1-4) bound to a non-inhibitory antibody fragment or to full-length Dkk1 shows that in both cases the ectodomain adopts a curved conformation that places the first three repeats at a similar height relative to the membrane. Thus, Wnts bound to either portion of the LRP6 ectodomain likely bear a similar spatial relationship to Frizzled co-receptors. PMID:22000856

  4. 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…

  5. 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…

  6. 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…

  7. Breaking the Mold: New Approaches for Higher Education in Tough Economic Times. Complete to Compete Briefing Paper

    ERIC Educational Resources Information Center

    Carey, Kevin

    2011-01-01

    Human capital is the key to economic development. Without highly-skilled workers, states and territories cannot attract the productive businesses they need. That makes higher education a key element of any governor's growth strategy. But many public colleges and universities are struggling to produce more graduates. Overall graduation rates often…

  8. 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…

  9. 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…

  10. 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…

  11. 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,…

  12. 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…

  13. 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. Massachusetts,…

  14. 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…

  15. 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); "Report from China"…

  16. Examining the Potential Impact of Full Tuition Fees on Mature Part-Time Students in English Higher Education

    ERIC Educational Resources Information Center

    Shaw, Angela

    2014-01-01

    This paper examines current part-time mature learners' views on the potential impact upon future students as full fees are introduced from 2012. It investigates the problems which part-time mature learners may face with the advent of student loans and subsequent debt, given that they are usually combining complex lives with their studies,…

  17. Full-Time Employed Students as University Consumers--Consequences and Triggers of Marketisation of Higher Education

    ERIC Educational Resources Information Center

    Mägi, Eve; Jaakson, Krista; Aidla, Anne; Kirss, Laura; Reino, Anne

    2012-01-01

    This article draws on a qualitative study of student employment patterns among students who both study and work full-time. In the study, 17 employed bachelor students at state-commissioned study places in three Estonian universities, 12 lecturers from the same universities, and 13 employers supervising those full-time students, were interviewed.…

  18. Higher rank Wilson loops in the {N}=2{SU}(N)\\times {SU}(N) conformal quiver

    NASA Astrophysics Data System (ADS)

    Fraser, Benjo

    2016-01-01

    In this note we compute the expectation value of a circular supersymmetric Wilson loop in the ‘higher rank’ totally symmetric and antisymmetric representations of {SU}(N) in the {\\hat{A}}1 quiver {N}=2 conformal field theory, using a matrix model. We discuss the connection with a recent conjecture stating that expectation values of observables in this sector are obtained from {N}=4 super Yang-Mills theory by a universal renormalization of the ’t Hooft coupling.

  19. Two tautomeric forms of 2-amino-5,6-dimethylpyrimidin-4-one.

    PubMed

    Hall, Victoria M; Bertke, Jeffery A; Swift, Jennifer A

    2016-06-01

    Derivatives of 4-hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto-enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H-keto tautomer in the solid state. Recrystallization of 2-amino-5,6-dimethyl-4-hydroxypyrimidine, C6H9N3O, from aqueous solution yielded triclinic crystals of the 1H-keto tautomer, denoted form (I). Though not apparent in the X-ray data, the IR spectrum suggests that small amounts of the 4-hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H-keto and the 3H-keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one-dimensional and three-dimensional hydrogen-bonding motifs, respectively. PMID:27256693

  20. 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.

  1. 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. PMID:25446802

  2. Factors Associated with Higher Sitting Time in General, Chronic Disease, and Psychologically-Distressed, Adult Populations: Findings from the 45 & Up Study

    PubMed Central

    Plotnikoff, Ronald C.; Costigan, Sarah A.; Short, Camille; Grunseit, Anne; James, Erica; Johnson, Natalie; Bauman, Adrian; D’Este, Catherine; van der Ploeg, Hidde P.; Rhodes, Ryan E.

    2015-01-01

    This study examined factors associated with higher sitting time in general, chronic disease, and psychologically-distressed, adult populations (aged ≥45 years). A series of logistic regression models examined potential socio-demographic and health factors associated with higher sitting (≥6hrs/day) in adults from the 45 and Up Study (n = 227,187), including four separate subsamples for analysis comprising those who had ever had heart disease (n = 26,599), cancer (n = 36,381), diabetes (n = 19,550) or psychological distress (n = 48,334). Odds of higher sitting were significantly (p<.01) associated with a number of factors across these groups, with an effect size of ORs≥1.5 observed for the high-income ≥$70,000AUD, employed full-time and severe physical limitations demographics. Identification of key factors associated with higher sitting time in this population-based sample will assist development of broad-based, public health and targeted strategies to reduce sitting-time. In particular, those categorized as being high-income earners, full-time workers, as well as those with severe physical limitations need to be of priority, as higher sitting appears to be substantial across these groups. PMID:26039739

  3. A television in the bedroom is associated with higher weekday screen time among youth with attention deficit hyperactivity disorder (ADD/ADHD)

    PubMed Central

    Lo, Charmaine B.; Waring, Molly E.; Pagoto, Sherry L.; Lemon, Stephenie C.

    2014-01-01

    Objective A TV in the bedroom has been associated with screen time in youth. Youth with attention deficit hyperactivity disorder (ADD/ADHD) have higher rates of screen time, but associations with bedroom TVs are unknown in this population. We examined the association of having a bedroom TV with screen time among youth with ADD/ADHD. Methods Data were from the 2007 National Survey of Children's Health. Youth 6–17 years whose parent/guardian reported a physician's diagnosis of ADD/ADHD (n = 7024) were included in the analysis. Parents/guardians reported the presence of a bedroom TV and average weekday TV screen time. Multivariate linear and logistic regression models assessed the effects of a bedroom on screen time. Results Youth with ADD/ADHD engaged in screen time with an average of 149.1 min/weekday and 59% had a TV in their bedroom. Adjusting for child and family characteristics, having a TV in the bedroom was associated with 25 minute higher daily screen time (95% CI: 12.8–37.4 min/day). A bedroom TV was associated with 32% higher odds of engaging in screen time for over 2 h/day (OR = 1.3; 95% CI: 1.0–1.7). Conclusion Future research should explore whether removing TVs from bedrooms reduces screen time among youth with ADD/ADHD. PMID:25599016

  4. Reliability and Validity of "Parents' Evaluation of Responsible Behaviors of 5-6 Year Old Children" Scale

    ERIC Educational Resources Information Center

    Polat, Ozgul; Dagal, Asude B.

    2013-01-01

    This study is aimed at developing a scale (Parents' Evaluation of Responsible Behaviors of 5-6 Year Old Children) for measuring parents' evaluation of their 5-6 year-old children's responsible behaviors. The construct validity of the scale was tested by Factor Analysis. Factor analysis determined that the scale can be clustered under 10 factors.…

  5. 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 ...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 5,6,7,8-Tetrahydropyrido[4,3-d]pyrimidines as novel class of potent and highly selective CaMKII inhibitors.

    PubMed

    Asano, Shigehiro; Komiya, Masafumi; Koike, Nobuyuki; Koga, Erina; Nakatani, Shogo; Isobe, Yoshiaki

    2010-11-15

    A novel series of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines containing substituted phenyl sulfonamide are synthesized and evaluated for their inhibitory activity against CaMKII. Substituents on the phenyl group had significant impact on CaMKII inhibition, in particular, the inhibitory activity of 8p was 25-fold higher than that of KN-93, a known CaMKII inhibitor. Michaelis-Menten analysis of a representative compound suggested that the synthesized pyrimidines are calmodulin non-competitive inhibitors. Finally, 8p exhibited more than 100-fold higher selectivity for CaMKII over five types of off-target kinases. PMID:20875738

  11. C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor.

    PubMed

    McLean, Thomas H; Chambers, James J; Parrish, Jason C; Braden, Michael R; Marona-Lewicka, Danuta; Kurrasch-Orbaugh, Deborah; Nichols, David E

    2006-07-13

    A conformationally restricted analogue of mescaline, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed using a 5-HT(2A) receptor homology model. The compound possessed 3-fold higher affinity and potency than and efficacy equal to that of mescaline at the 5-HT(2A) receptor. The new analogue substituted fully for LSD in drug discrimination studies and was 5-fold more potent than mescaline. Resolution of this analogue into its enantiomers corroborated the docking experiments, showing the R-(+) isomer to have higher affinity and potency and to have efficacy similar to that of mescaline at the 5-HT(2A) receptor. PMID:16821786

  12. 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…

  13. 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…

  14. 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:…

  15. Part-Time Faculty Personnel Management Policies. American Council on Education/Macmillan Series on Higher Education.

    ERIC Educational Resources Information Center

    Biles, George E.; Tuckman, Howard P.

    A framework for integrating part-time college faculty into an existing institutional structure is presented. Suggestions are offered on ways that department and division heads can make personnel policies that meet both the part-timer's need for fairness, certainty, and structure, and the college's need for flexibility and order. Policies are…

  16. 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…

  17. 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…

  18. Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.

    PubMed

    Napadow, Vitaly; Dhond, Rupali; Park, Kyungmo; Kim, Jieun; Makris, Nikos; Kwong, Kenneth K; Harris, Richard E; Purdon, Patrick L; Kettner, Norman; Hui, Kathleen K S

    2009-08-01

    Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (SII, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation--consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our study demonstrates that acupuncture modulation of brainstem structures can be studied non-invasively in humans, allowing for comparison to animal studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations. PMID:19345268

  19. A Sequential Linear Quadratic Approach for Constrained Nonlinear Optimal Control with Adaptive Time Discretization and Application to Higher Elevation Mars Landing Problem

    NASA Astrophysics Data System (ADS)

    Sandhu, Amit

    A sequential quadratic programming method is proposed for solving nonlinear optimal control problems subject to general path constraints including mixed state-control and state only constraints. The proposed algorithm further develops on the approach proposed in [1] with objective to eliminate the use of a high number of time intervals for arriving at an optimal solution. This is done by introducing an adaptive time discretization to allow formation of a desirable control profile without utilizing a lot of intervals. The use of fewer time intervals reduces the computation time considerably. This algorithm is further used in this thesis to solve a trajectory planning problem for higher elevation Mars landing.

  20. Comprehensive Synthesis of Monohydroxy-Cucurbit[n]urils (n = 5, 6, 7, 8): High Purity and High Conversions.

    PubMed

    Ayhan, Mehmet M; Karoui, Hakim; Hardy, Micaël; Rockenbauer, Antal; Charles, Laurence; Rosas, Roselyne; Udachin, Konstantin; Tordo, Paul; Bardelang, David; Ouari, Olivier

    2015-08-19

    We describe a photochemical method to introduce a single alcohol function directly on cucurbit[n]urils (n = 5, 6, 7, 8) with conversions of the order 95-100% using hydrogen peroxide and UV light. The reaction was easily scaled up to 1 g for CB[6] and CB[7]. Spin trapping of cucurbituril radicals combined with MS experiments allowed us to get insights about the reaction mechanism and characterize CB[5], CB[6], CB[7], and CB[8] monofunctional compounds. Experiments involving (18)O isotopically labeled water indicated that the mechanism was complex and showed signs of both radical and ionic intermediates. DFT calculations allowed estimating the Bond Dissociation Energies (BDEs) of each hydrogen atom type in the CB series, providing an explanation of the higher reactivity of the "equatorial" C-H position of CB[n] compounds. These results also showed that, for CB[8], direct functionalization on the cucurbituril skeleton is more difficult because one of the methylene hydrogen atoms (Hb) has its BDE lowering within the series and coming close to that of Hc, thus opening the way to other types of free radicals generated on the CB[8] skeleton leading to several side products. Yet CB[5]-(OH)1 and CB[8]-(OH)1, the first CB[8] derivative, were obtained in excellent yields thanks to the soft method presented here. PMID:26197228

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

    PubMed

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

    2015-12-17

    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

  2. Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase.

    PubMed

    Ho, Melisa W Y; Yang, Xiaonian; Carew, Mark A; Zhang, Tong; Hua, Len; Kwon, Yong-Uk; Chung, Sung-Kee; Adelt, Stephan; Vogel, Günter; Riley, Andrew M; Potter, Barry V L; Shears, Stephen B

    2002-03-19

    Regulation of Cl(-) channel conductance by Ins(3,4,5,6)P(4) provides receptor-dependent control over salt and fluid secretion, cell volume homeostasis, and electrical excitability of neurones and smooth muscle. Ignorance of how Ins(3,4,5,6)P(4) is synthesized has long hindered our understanding of this signaling pathway. We now show Ins(3,4,5,6)P(4) synthesis by Ins(1,3,4,5,6)P(5) 1-phosphatase activity by an enzyme previously characterized as an Ins(3,4,5,6)P(4) 1-kinase. Rationalization of these phenomena with a ligand binding model unveils Ins(1,3,4)P(3) as not simply an alternative kinase substrate, but also an activator of Ins(1,3,4,5,6)P(5) 1-phosphatase. Stable overexpression of the enzyme in epithelial monolayers verifies its physiological role in elevating Ins(3,4,5,6)P(4) levels and inhibiting secretion. It is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases. PMID:11909533

  3. 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

  4. 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. PMID:27564449

  5. All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

    NASA Astrophysics Data System (ADS)

    Keddie, Neil S.; Slawin, Alexandra M. Z.; Lebl, Tomas; Philp, Douglas; O'Hagan, David

    2015-06-01

    The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C-F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (˜2.77 Å) are longer than the vicinal Fax···Feq­ distances (˜2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.

  6. Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.

    PubMed

    Fan, Maomin; Duesler, Eileen N; Nöth, Heinrich; Paine, Robert T

    2010-03-15

    The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6-pentamethyl-2-aminoborazine have been examined. An amine alane adduct (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH] (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6) have been isolated. Compounds 1, 2, 4-6 have been spectroscopically characterized, and single crystal X-ray diffraction structure determinations have been completed for 1-4 and 6. The molecular chemistry provides insight into the reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon pyrolysis, produces AlN/BN composite ceramic materials. PMID:20158196

  7. Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase

    PubMed Central

    Brehm, Maria A.; Schenk, Tobias M. H.; Zhou, Xuefei; Fanick, Werner; Lin, Hongying; Windhorst, Sabine; Nalaskowski, Marcus M.; Kobras, Mario; Shears, Stephen B.; Mayr, Georg W.

    2007-01-01

    InsP6 is an intracellular signal with several proposed functions that is synthesized by IP5K [Ins(1,3,4,5,6)P5 2-kinase]. In the present study, we overexpressed EGFP (enhanced green fluorescent protein)–IP5K fusion proteins in NRK (normal rat kidney), COS7 and H1299 cells. The results indicate that there is spatial microheterogeneity in the intracellular localization of IP5K that could also be confirmed for the endogenous enzyme. This may facilitate changes in InsP6 levels at its sites of action. For example, overexpressed IP5K showed a structured organization within the nucleus. The kinase was preferentially localized in euchromatin and nucleoli, and co-localized with mRNA. In the cytoplasm, the overexpressed IP5K showed locally high concentrations in discrete foci. The latter were attributed to stress granules by using mRNA, PABP [poly(A)-binding protein] and TIAR (TIA-1-related protein) as markers. The incidence of stress granules, in which IP5K remained highly concentrated, was further increased by puromycin treatment. Using FRAP (fluorescence recovery after photobleaching) we established that IP5K was actively transported into the nucleus. By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K. PMID:17705785

  8. 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. PMID:22519761

  9. Fe L-shell lines from n (n=4, 5, 6) to 2 transitions

    NASA Astrophysics Data System (ADS)

    Chen, H.; Beiersdorfer, P.; Brown, G.; Behar, E.

    2003-03-01

    Fe L-shell emission lines at wavelengths less than 10 angstroms come from n (n great than 3) to 2 transitions. These lines embed information such as electron density and temperature that is of fundamental importance to understanding the physics of astrophysical objects. Unresolved by previous x-ray observatories, these low wavelength Fe lines are clearly observable by Chandra and XMM x-ray satellites. To meet the needs of using these lines as diagnostics, we have studied the n to 2 transitions (n = 4, 5, 6) Fe L-shell lines using the atomic codes HULLAC and FAC. Using the LLNL electron beam ion trap, we also made laboratory measurements for this wavelength region, following the success of our Fe L-shell emission lines for the 3-2 transitions (Brown et al, APJ supp. 2002). Our measurements and their comparison with code simulations will be reported, together with a discussion of the possible use of these low wavelength lines as diagnostics for astrophysics. This work was performed under the auspices of the U.S. DOE by LLNL under contract No. W-7405-Eng-48 and supported by NASA SARA grants to LLNL, GSFC, and Columbia University.

  10. Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats

    PubMed Central

    Pacurari, Maricica; Xing, Dongqi; Hilgers, Rob H. P.; Guo, Yuan Yuan; Yang, Zhengqin

    2013-01-01

    Endothelial dysfunction is prevalent in chronic kidney disease. This study tested the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague-Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx, EC (1.5 × 106 cells/rat) or vehicle were transfused intravenously. One week later, vascular reactivity of mesenteric artery was assessed on a wire myograph. Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum vasodilation were impaired by Nx and improved by EC transfusion. Using selective pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that the negative effect of Nx on endothelial function and rescue by EC transfusion are, at least in part, endothelial nitric oxide synthase mediated. Plasma asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion, whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was decreased by Nx and restored by EC transfusion. Immunohistochemical staining confirmed that local expression of DDAH1 is decreased by Nx and increased by EC transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium-dependent vascular dysfunction by regulating DDAH1 expression and enhancing endothelial nitric oxide synthase activity. These results suggest that EC-based therapy could provide a novel therapeutic strategy to improve vascular function in chronic kidney disease. PMID:23955716

  11. Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR.

    PubMed

    Clifford, Gary M; Vaccarella, Salvatore; Franceschi, Silvia; Tenet, Vanessa; Umulisa, M Chantal; Tshomo, Ugyen; Dondog, Bolormaa; Vorsters, Alex; Tommasino, Massimo; Heideman, Daniëlle A M; Snijders, Peter J F; Gheit, Tarik

    2016-08-01

    GP5+/6+-based PCR followed by reverse line blot hybridization (GP5+/6+RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5+/6+RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5+/6+RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5+/6+RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5+/6+RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5+/6+RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5+/6+RLB than for those negative for the same type by GP5+/6+RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5+/6+RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5+/6+RLB, suggesting the existence of masking effects due to competition for GP5+/6+ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination. PMID:27225411

  12. Progress integrating ID-TIMS U-Pb geochronology with accessory mineral geochemistry: towards better accuracy and higher precision time

    NASA Astrophysics Data System (ADS)

    Schoene, B.; Samperton, K. M.; Crowley, J. L.; Cottle, J. M.

    2012-12-01

    It is increasingly common that hand samples of plutonic and volcanic rocks contain zircon with dates that span between zero and >100 ka. This recognition comes from the increased application of U-series geochronology on young volcanic rocks and the increased precision to better than 0.1% on single zircons by the U-Pb ID-TIMS method. It has thus become more difficult to interpret such complicated datasets in terms of ashbed eruption or magma emplacement, which are critical constraints for geochronologic applications ranging from biotic evolution and the stratigraphic record to magmatic and metamorphic processes in orogenic belts. It is important, therefore, to develop methods that aid in interpreting which minerals, if any, date the targeted process. One promising tactic is to better integrate accessory mineral geochemistry with high-precision ID-TIMS U-Pb geochronology. These dual constraints can 1) identify cogenetic populations of minerals, and 2) record magmatic or metamorphic fluid evolution through time. Goal (1) has been widely sought with in situ geochronology and geochemical analysis but is limited by low-precision dates. Recent work has attempted to bridge this gap by retrieving the typically discarded elution from ion exchange chemistry that precedes ID-TIMS U-Pb geochronology and analyzing it by ICP-MS (U-Pb TIMS-TEA). The result integrates geochemistry and high-precision geochronology from the exact same volume of material. The limitation of this method is the relatively coarse spatial resolution compared to in situ techniques, and thus averages potentially complicated trace element profiles through single minerals or mineral fragments. In continued work, we test the effect of this on zircon by beginning with CL imaging to reveal internal zonation and growth histories. This is followed by in situ LA-ICPMS trace element transects of imaged grains to reveal internal geochemical zonation. The same grains are then removed from grain-mount, fragmented, and

  13. Synthesis and anticancer activities of 4-(4-substituted piperazin)-5,6,7-trialkoxy quinazoline derivatives.

    PubMed

    Zhang, Ying; Huang, Yin-Jiu; Xiang, Hong-Mei; Wang, Pei-Yi; Hu, De-Yu; Xue, Wei; Song, Bao-An; Yang, Song

    2014-05-01

    A series of 4-(4-substituted piperazin)-5,6,7-trialkoxy quinazoline was prepared by conventional heating methods. Among these compounds, the crystal structure of compound 10o (CCDC: 916922) was determined by X-ray crystallography. Bioassay results showed that most target compounds had certain inhibition activities against proliferation of tumor cells, and some compounds even had good broad-spectrum inhibition activities. The ethoxyl series of compounds possessed higher inhibition activities against tumor cells than the methoxyl series of compounds. Bioactivity tests showed that the IC50 values of compound 10s against PC3, MGC803, A375, and A549 cells were 1.8, 2.8, 1.3, and 2.9 μΜ, respectively, which were much higher than those of commercial gefitinib (7.2, 7.6, 7.2, and 9.8 μM, respectively). Conversely, the IC50 values of compound 10s were very low against NH3T3, indicating only weak effect on normal cells as also proven by lactate dehydrogenase and acridine orange/ethidium bromide staining. Analyses of cell configuration and cell cycle revealed that compound 10s possibly caused cells to remain at G0/G1 phase by inhibiting cell proliferation for 24 h. Compound 10s also inhibited the phosphorylation of ERK1/2 and P38 with obvious concentration dependence. Thus, these compounds can inhibit the proliferation of A549 cells through the interruption of ERK1/2 and P38signaling pathways. PMID:24675177

  14. Substitution effects on nonlinear optical activity of (X-methylphenyl)-5-nitro-6-amino-3-pyridinecarboxmide (X=2,3,4,5,6): A DFT approach

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    The substitution effects on the first order hyperpolarizability value of (X-methylphenyl)-5-nitro-6-amino-3-pyridinecarboxmide (X-MPNAPC),{X=2,3,4,5,6}molecule was calculated with the aid of density functional theory calculations. The optimized molecular structure of urea and (X-methylphenyl)-5-nitro-6-amino-3-pyridinecarboxmide (X-MPNAPC), {X=2,3,4,5,6} were predicted by the DFT/B3LYP method with cc-pVTZ basis set. The higher first order hyperpolarizability values were obtained for all molecules compared with the urea, which confirm that the higher nonlinear optical activity of the molecules. The frontier molecular orbitals (FMOs) analysis was carried out and their related molecular properties were calculated. The higher first order hyperpolarizability value was obtained for 4-MPNAPC molecule compared with other molecules, which indicates that the lower energy gap and extended π-conjugated bridge between the donor and acceptor group leads to the higher NLO activity of the molecule. Hence, this present investigation paves the way for designing the new organic NLO materials.

  15. Late time acceleration of the 3-space in a higher dimensional steady state universe in dilaton gravity

    NASA Astrophysics Data System (ADS)

    Akarsu, Özgür; Dereli, Tekin

    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.

  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. Proprotein convertase 5/6 cleaves platelet-derived growth factor A in the human endometrium in preparation for embryo implantation.

    PubMed

    Paule, Sarah; Nebl, Thomas; Webb, Andrew I; Vollenhoven, Beverley; Rombauts, Luk J F; Nie, Guiying

    2015-03-01

    Establishment of endometrial receptivity is vital for successful embryo implantation. Proprotein convertase 5/6 (referred to as PC6) is up-regulated in the human endometrium specifically at the time of epithelial receptivity. PC6, a serine protease of the proprotein convertase family, plays an important role in converting precursor proteins into their active forms through specific proteolysis. The proform of platelet-derived growth factor A (pro-PDGFA) requires PC cleavage to convert to the active-PDGFA. We investigated the PC6-mediated activation of PDGFA in the human endometrium during the establishment of receptivity. Proteomic analysis identified that the pro-PDGFA was increased in the conditioned medium of HEC1A cells in which PC6 was stably knocked down by small interfering RNA (PC6-siRNA). Western blot analysis demonstrated an accumulation of the pro-PDGFA but a reduction in the active-PDGFA in PC6-siRNA cell lysates and medium compared with control. PC6 cleavage of pro-PDGFA was further confirmed in vitro by incubation of recombinant pro-PDGFA with PC6. Immunohistochemistry revealed cycle-stage-specific localization of the active-PDGFA in the human endometrium. During the non-receptive phase, the active-PDGFA was barely detectable. In contrast, it was localized specifically to the apical surface of the luminal and glandular epithelium in the receptive phase. Furthermore, the active-PDGFA was detected in uterine lavage with levels being significantly higher in the receptive than the non-receptive phase. We thus identified that the secreted PDGFA may serve as a biomarker for endometrial receptivity. This is also the first study demonstrating that the active-PDGFA localizes to the apical surface of the endometrium during receptivity. PMID:25429785

  18. 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). PMID:27121015

  19. 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.

  20. 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. PMID:26838417

  1. Achievements and Planned Programmes of Activities of The Csg.5/6 "geodynamics of Northern Carpathians"

    NASA Astrophysics Data System (ADS)

    Zablotskyj, F.; Tretyak, K.

    Within the programme of the regional group CSG.5/6 "Geodynamics of Northern Carpathians", the following main lines are carried out. (1) Geodetic and geophysical investigations of the recent crustal movements and geophysical analysis of deep struc- ture on the Carpathian geodynamic test field. (2) Subsequent study of geological struc- tures in the region of Northern Carpathians. On the initiative of the Main Astronomical Observatory, the National Space Agency and the Aerogeodetic Enterprise of Ukraine two permanent GPS stations, UZHL and SULP, were being established during last 1.5 years. The first one is situated in the zone of Transcarpathian flexure (Uzhgorod, University) and the second one - in the west of East-European plate (the Precarpathi- ans, Lviv, Polytechnic University). In addition to the long-term project "Restoration of Ukrainian-Polish complex geophysical station at Pip Ivan Mount in Charnohora (Ukrainian Carpathians)", the following actions are planned for 2002-2004. (1) To carry out the complex geodetic, geophysical, geological and geomorphological in- vestigations in this region, which is less studied in comparison with other areas in Carpathians. The comparison of simultaneous appearance of geophysical processes in these regions will allow detect a degree of influence of endogenic, exogenic, and antro- pogenig factors on present day hydro-geological processes in the whole Carpathian region. (2) To create a network of permanent stations for the complex geophysical and geodynamic monitoring, which will include measurements of intensity of Earth's surface deformation field, remote photogrammetric measurements of intensity of de- structive and shift processes, the determination of parameters of gravity and mag- netic fields, seismic and electrometric measurements, spectral analysis of space im- ages for quality and quantity estimations of technogenic and antropogenic activity, generalization of data on evolution and dynamics of river systems and

  2. The 2012 MW5.6 earthquake in the vicinity of the city of Sofia

    NASA Astrophysics Data System (ADS)

    Simeonova, Stela; Solakov, Dimcho; Aleksandrova, Irena; Dimitrova, Liliya; Popova, Iliana; Raykova, Plamena

    2013-04-01

    The territory of Bulgaria represents a typical example of high seismic risk area in the eastern part of the Balkan Peninsula. The neotectonic movements on the Balkan Peninsula were controlled by extensional collapse of the Late Alpin orogen, and were influenced by extension behind the Aegean arc and by the complicated vertical and horizontal movements in the Pannonian region. The city of Sofia is the capital of Bulgaria. It is situated in the centre of the Sofia seismic zone that is the most populated (more than 1.2 mil. inhabitants), industrial and cultural region of Bulgaria that faces considerable earthquake risk. Seismicity in the zone is related mainly to the marginal neotectonic faults of Sofia graben. The available historical documents prove the occurrence of destructive earthquakes during the 15th-18th centuries in the Sofia zone. In 19th century the city of Sofia has experienced two strong earthquakes: the 1818 earthquake with epicentral intensity I0=8-9 MSK and the 1858 earthquake with I0=IX-X MSK64. The 1858 earthquake caused heavy destruction in the town of Sofia and the appearance of thermal springs in the western part of the town. After a quiescence of about 50 years a strong event with M=6.5 occurred in 1905 near the western marginal part of the Sofia zone. During the 20th century the strongest event occurred in the vicinity of the city of Sofia is the 1917 earthquake with MS=5.3 (I0=7-8 MSK64). The earthquake caused a lot of damages in the town and changed the capacity of the thermal mineral springs in Sofia and the surrounding villages. The earthquake was felt in an area of 50000 km2 and followed by aftershocks, which lasted more than one year. Almost a century later (95 years) an earthquake of moment magnitude 5.6 hit Sofia seismic zone, on May 22nd, 2012, at 25 km south west of the city of Sofia. This shallow earthquake was largely felt in the region and up to Greece, FYROM, Serbia and Romania. No severe injuries have been reported so far, though

  3. Study of a conjugate Pc 5-6 magnetic and absorption pulsation event at subauroral latitudes in the morning sector

    SciTech Connect

    Oksman, J.; Rosenberg, T.J. ); Lanzerotti, L.J.; MaClennan, C.G. ); Singer, H.J. )

    1988-06-01

    An interval of long-period hydromagnetic wave activity occurring in the decay phase of a magnetic storm has been studied using ground-based magnetic field and cosmic noise absorption data recorded at L {approx lt} 4.2. There is some evidence in the data for the wave frequencies to be {approximately} 0.2 mHz lower at L {approximately} 3.0-3.2 than at L {approximately} 3.8-4.2. The low wave frequencies are inconsistent with resonant oscillations of the field lines within the L shell range and probable magnetosphere plasma density conditions of observation. The waves were observed to propagate westward over at least 3 hours of local time, near dawn. An azimuthal wave number m {approx} 9 and a westward phase velocity varying from {approximately} 2.5 to {approximately} 7.5 km s{sup {minus}1} at 55{degree} magnetic latitude characterized the event. The low azimuthal phase velocities make it unlikely that the waves were generated by the Kelvin-Helmholtz instability on the magnetopause. These Pc 5-6 waves appear to be odd mode, locally driven nonresonant oscillations. The ULF wave generation and propagation were most likely located on geomagnetic field lines in the range 3.5 {approx lt} L {approx lt} 6 in the region of hot storm time plasma outside the plasmapause where a gradient in particle precipitation flux was also observed. Neither the drift mirror instability nor the compressional drift wave instability appears to be a likely source for these waves. Modulation by the ULF waves of the pitch angle diffusion of energetic electrons injected into outer radiation zone during the magnetospheric storm is suggested to account for the cosmic noise absorption pulsations observed outside the plasmapause. Irregular plasma density gradients in this region, inferred from the propagation characteristics of whistler mode VLF signals, may have caused the observed H-D plane wave polarization variations.

  4. Synthesis of 5,6-dihydro-4H-benzo[d]isoxazol-7-one and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-one derivatives as potential Hsp90 inhibitors.

    PubMed

    Musso, Loana; Cincinelli, Raffaella; Giannini, Giuseppe; Manetti, Fabrizio; Dallavalle, Sabrina

    2015-11-01

    A novel class of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to investigate the affinity toward Hsp90 protein. The synthetic route was based on a 1,3-dipolar cycloaddition of nitriloxides, generated in situ from suitable benzaldoximes, with 2-bromocyclohex-2-enones or 3-bromo-5,6-dihydro-1H-pyridin-2-ones. Whereas all the compounds bearing a benzamide group on the bicyclic scaffold were devoid of activity, the derivatives carrying a resorcinol-like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme. PMID:25855505

  5. The Cytochrome b5 dependent C-5(6) sterol desaturase DES5A from the endoplasmic reticulum of Tetrahymena thermophila complements ergosterol biosynthesis mutants in Saccharomyces cerevisiae

    PubMed Central

    Poklepovich, Tomas J.; Rinaldi, Mauro A.; Tomazic, Mariela L.; Favale, Nicolas O.; Turkewitz, Aaron P.; Nudel, Clara B.; Nusblat, Alejandro D.

    2012-01-01

    Tetrahymena thermophila is a free-living ciliate with no exogenous sterol requirement. However, it can perform several modifications on externally added sterols including desaturation at C5(6), C7(8), and C22(23). Sterol desaturases in Tetrahymena are microsomal enzymes that require Cyt b5, Cyt b5 reductase, oxygen, and reduced NAD(P)H for their activity, and some of the genes encoding these functions have recently been identified. The DES5A gene encodes a C-5(6) sterol desaturase, as shown by gene knockout in Tetrahymena. To confirm and extend that result, and to develop new approaches to gene characterization in Tetrahymena, we have now, expressed DES5A in Saccharomyces cerevisiae. The DES5A gene was codon optimized and expressed in a yeast mutant, erg3Δ, which is disrupted for the gene encoding the S. cerevisiae C-5(6) sterol desaturase ERG3. The complemented strain was able to accumulate 74% of the wild type level of ergosterol, and also lost the hypersensitivity to cycloheximide associated with the lack of ERG3 function. C-5(6) sterol desaturases are expected to function at the endoplasmic reticulum. Consistent with this, a GFP-tagged copy of Des5Ap was localized to the endoplasmic reticulum in both Tetrahymena and yeast. This work shows for the first time that both function and localization are conserved for a microsomal enzyme between ciliates and fungi, notwithstanding the enormous evolutionary distance between these lineages. The results suggest that heterologous expression of ciliate genes in S. cerevisiae provides a useful tool for the characterization of genes in Tetrahymena, including genes encoding membrane protein complexes. PMID:22982564

  6. Habit modification of 5,6-dimethyl-1H-benzotriazole in the presence of nonionic triblock copolymers

    NASA Astrophysics Data System (ADS)

    Molloy, Meghan R.; Partch, Richard

    2013-06-01

    The effects of different nonionic surfactants on the habit modification of 5,6-dimethyl-1H-benzotriazole (5,6-DMBTA) were evaluated. Three different triblock copolymers, Pluronic® F-127, Pluronic® L44NF, and Pluronic® P-123 were selected as nonionic surfactants. Crystallization was achieved by pH adjustment in an aqueous solution with or without the presence of surfactants. Pluronic® P-123 was found to have the most dramatic effect in changing the crystal habit of 5,6-DMBTA from needles to platelets. The surfactant with a smaller hydrophobic block, Pluronic® L44NF, or the one with a larger hydrophilic block, Pluronic® F-127, yield only shorter needles for the crystal habit. This indicates that both blocks of a surfactant backbone have an impact on habit modification. Analytical data confirmed that none of the three surfactants were incorporated into the crystal lattice of 5,6-DMBTA after crystallization. All the habit modified crystals have the same crystal form as the original 5,6-DMBTA crystal sample, indicating that solely a habit modifying process took place.

  7. 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

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

    PubMed

    Grover, P L; Sims, P

    1965-08-01

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

  9. Higher-order in time "quasi-unconditionally stable" ADI solvers for the compressible Navier-Stokes equations in 2D and 3D curvilinear domains

    NASA Astrophysics Data System (ADS)

    Bruno, Oscar P.; Cubillos, Max

    2016-02-01

    This paper introduces alternating-direction implicit (ADI) solvers of higher order of time-accuracy (orders two to six) for the compressible Navier-Stokes equations in two- and three-dimensional curvilinear domains. The higher-order accuracy in time results from 1) An application of the backward differentiation formulae time-stepping algorithm (BDF) in conjunction with 2) A BDF-like extrapolation technique for certain components of the nonlinear terms (which makes use of nonlinear solves unnecessary), as well as 3) A novel application of the Douglas-Gunn splitting (which greatly facilitates handling of boundary conditions while preserving higher-order accuracy in time). As suggested by our theoretical analysis of the algorithms for a variety of special cases, an extensive set of numerical experiments clearly indicate that all of the BDF-based ADI algorithms proposed in this paper are "quasi-unconditionally stable" in the following sense: each algorithm is stable for all couples (h , Δt)of spatial and temporal mesh sizes in a problem-dependent rectangular neighborhood of the form (0 ,Mh) × (0 ,Mt). In other words, for each fixed value of Δt below a certain threshold, the Navier-Stokes solvers presented in this paper are stable for arbitrarily small spatial mesh-sizes. The second-order formulation has further been rigorously shown to be unconditionally stable for linear hyperbolic and parabolic equations in two-dimensional space. Although implicit ADI solvers for the Navier-Stokes equations with nominal second-order of temporal accuracy have been proposed in the past, the algorithms presented in this paper are the first ADI-based Navier-Stokes solvers for which second-order or better accuracy has been verified in practice under non-trivial (non-periodic) boundary conditions.

  10. Real-time object recognition in multidimensional images based on joined extended structural tensor and higher-order tensor decomposition methods

    NASA Astrophysics Data System (ADS)

    Cyganek, Boguslaw; Smolka, Bogdan

    2015-02-01

    In this paper a system for real-time recognition of objects in multidimensional video signals is proposed. Object recognition is done by pattern projection into the tensor subspaces obtained from the factorization of the signal tensors representing the input signal. However, instead of taking only the intensity signal the novelty of this paper is first to build the Extended Structural Tensor representation from the intensity signal that conveys information on signal intensities, as well as on higher-order statistics of the input signals. This way the higher-order input pattern tensors are built from the training samples. Then, the tensor subspaces are built based on the Higher-Order Singular Value Decomposition of the prototype pattern tensors. Finally, recognition relies on measurements of the distance of a test pattern projected into the tensor subspaces obtained from the training tensors. Due to high-dimensionality of the input data, tensor based methods require high memory and computational resources. However, recent achievements in the technology of the multi-core microprocessors and graphic cards allows real-time operation of the multidimensional methods as is shown and analyzed in this paper based on real examples of object detection in digital images.

  11. 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.

  12. 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

  13. Inhibition of bovine viral diarrhea virus RNA synthesis by thiosemicarbazone derived from 5,6-dimethoxy-1-indanone.

    PubMed

    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

    2011-06-01

    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

  14. Kinetically Blocked Stable 5,6:12,13-Dibenzozethrene: A Laterally π-Extended Zethrene with Enhanced Diradical Character.

    PubMed

    Yadav, Priya; Das, Soumyajit; Phan, Hoa; Herng, Tun Seng; Ding, Jun; Wu, Jishan

    2016-06-17

    Although the ground-state and physical properties of zethrene and recently invented 1,2:8,9-dibenzozethrene have been well studied, the other dibenzozethrene isomer, i.e., 5,6:12,13-dibenzozethrene, remained unexplored. A short synthetic route to a kinetically blocked stable 5,6:12,13-dibenzozethrene derivative 5 is presented. The ground state is found to be open-shell singlet experimentally, and the theoretical y0 was enhanced to 0.414, which corroborates nicely with the experimental and theoretical singlet-triplet energy gap. PMID:27227758

  15. 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. PMID:26930513

  16. 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. PMID:27368788

  17. 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.…

  18. 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

  19. Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6.

    PubMed

    Duan, Xinyuan; Yang, Yan; Chen, Yu-Hung; Arenz, Jacqueline; Rangi, Gurdish K; Zhao, Xiaolan; Ye, Hong

    2009-03-27

    The evolutionarily conserved structural maintenance of chromosome (SMC) proteins forms the core structures of three multisubunit complexes as follows: cohesin, condensin, and the Smc5/6 complex. These complexes play crucial roles in different aspects of chromosomal organization, duplication, and segregation. Although the architectures of cohesin and condensin are better understood, that of the more recently identified Smc5/6 complex remains to be elucidated. We have previously shown that the Smc5/6 complex of Saccharomyces cerevisiae contains Smc5, Smc6, and six non-SMC elements (Nse1-6). In this study, we investigated the architecture of the budding yeast Smc5/6 complex employing the yeast two-hybrid assay as well as in vitro biochemical approaches using purified recombinant proteins. These analyses revealed that Smc5 and Smc6 associate with each other at their hinge regions and constitute the backbone of the complex, whereas the Nse1-6 subunits form three distinct subcomplexes/entities that interact with different regions of Smc5 and Smc6. The Nse1, -3, and -4 subunits form a stable subcomplex that binds to the head and the adjacent coiled-coil region of Smc5. Nse2 binds to the middle of the coiled-coil region of Smc5. Nse5 and Nse6 interact with each other and, as a heterodimer, bind to the hinge regions of Smc5 and Smc6. These findings provide new insights into the structures of the Smc5/6 complex and lay the foundation for further investigations into the mechanism of its functions. PMID:19141609

  20. Selective and effective binding of pillar[5,6]arenes toward secondary ammonium salts with a weakly coordinating counteranion.

    PubMed

    Li, Chunju; Shu, Xiaoyan; Li, Jian; Fan, Jiazeng; Chen, Zhenxia; Weng, Linhong; Jia, Xueshun

    2012-08-17

    The selective and effective binding of secondary ammoniums with a weakly coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF) counteranion by per-ethylated pillar[5,6]arenes is reported. The construction of a first pillararene-based self-sorting system consisting of two wheels and two axles is also described. PMID:22866893

  1. Cyg X-1: A return to the pre-1971 intensity level and a 5.6-day modulation

    NASA Technical Reports Server (NTRS)

    Holt, S. S.; Kaluzienski, L. J.; Boldt, E. A.; Serlemitsos, P. J.

    1976-01-01

    Ariel-5 all sky monitor data on Cyg X-1 X-ray intensity increase during 1975 are analyzed. Data cover rise, maximum, and decay variability of the constellation. Special attention was given to the failure of the increase to decay over the specified period of 5.6 days.

  2. A Study on the Relationship between the Rhythm and Mathematics Skills of 5-6 Year Old Children

    ERIC Educational Resources Information Center

    Mertoglu, Ercan

    2010-01-01

    This is a relational scan study aiming to question the relationship between rhythm skills which are the most fundamental element in musical development and mathematics ability. Also within the general aims of the study is to examine whether this relationship varies with respect to the personal characteristics of 5-6 year olds. It has been…

  3. Lack of mutagenicity of the fungicide 2,4,5,6-tetrachloroisophthalonitrile in the Ames Salmonella/microsome test

    SciTech Connect

    Wei, C.I.

    1982-01-01

    The fungicide 2,4,5,6-tetrachloroisophthalonitrile, detected from a coal fly ash sample, was found to be not mutagenic to five Salmonella typhimurium tester strains. Incorporation of either a liver or a kidney activation system did not increase the mutagenic activity of the fungicide.

  4. Cs[H2NB2(C6F5)6] Featuring an Unequivocal 16-Coordinate Cation.

    PubMed

    Pollak, David; Goddard, Richard; Pörschke, Klaus-Richard

    2016-08-01

    Cesium bis(perfluoro-triphenylborane)amide, Cs[H2NB2(C6F5)6] (1), has been prepared by the reaction of sodium salt and CsF in dichloromethane and water. The compound is exceptional for a [H2NB2(C6F5)6](-) salt in that it contains a monatomic solute-free cation. Determination of the molecular structure revealed a novel C2 symmetrical conformation of the weakly coordinating [H2NB2(C6F5)6](-) anion, which gives rise to an unprecedented 16-coordinate (CN 16) Cs(+) cation in a likewise unprecedented tetracosahedral arrangement of F atoms. The poor solubility of 1 allows nearly quantitative separation of Cs(+) from water, which suggests potential applications as an effective (134/137)Cs remover from nuclear waste solutions, administration as an antidote for (134/137)Cs poisoning, and use for (131/137)Cs radiotherapy (brachytherapy). Rb[H2NB2(C6F5)6]·CH2Cl2 (2) has also been characterized, featuring two inequivalent Rb(+) cations having CN 10, one of which involves Rb(+)(η(2)-Cl2CH2)2 coordination. PMID:27267866

  5. 5-Bromo (or chloro)-6-azido-5,6-dihydro-2' -deoxyuridine and -thymidine derivatives with potent antiviral activity.

    PubMed

    Kumar, Rakesh

    2002-02-11

    Synthesis, antiviral, and cytotoxic activities of 5-bromo (or chloro)-6-azido-5,6-dihydro-2' -deoxyuridine (4,5) and -thymidine (6,7) are reported. Compounds 4 and 5 exhibited a broad spectrum of antiherpes activity against (HSV-1, HSV-2, HCMV, and VZV). PMID:11814776

  6. 77 FR 17386 - Significant New Use Rule for Hexabromocyclododecane and 1,2,5,6,9,10-Hexabromocyclododecane

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-26

    ...EPA is proposing a significant new use rule (SNUR) under section 5(a)(2) of the Toxic Substances Control Act (TSCA) for two chemical substances: Hexabromocyclododecane (Chemical Abstracts Service Registry Number (CASRN) 25637-99-4) and 1,2,5,6,9,10- hexabromocyclododecane (CASRN 3194-55-6), hereinafter collectively referred to as HBCD. This proposed rule would designate ``use in consumer......

  7. Janus all-cis-1,2,3,4,5,6-Hexafluorocyclohexane: A Molecular Motif for Aggregation-Induced Enhanced Polarization.

    PubMed

    Pratik, Saied Md; Nijamudheen, Abdulrahiman; Datta, Ayan

    2016-08-01

    Recently synthesized all-cis-1,2,3,4,5,6-hexafluorocyclohexane is the least stable among all possible configurational isomers of 1,2,3,4,5,6-hexafluorocyclohexane. This molecule has a remarkably large dipole moment (6.2 D) as well as high facial polarization. Solid-state, dispersion-corrected DFT (DFT-D3) calculations are performed on the crystalline phase of all-cis-1,2,3,4,5,6- hexafluorocyclohexane, which reveal that dispersion interactions play a crucial role in its stabilization. A number of thermodynamically favorable orientations of dimers, trimers and tetramers are demonstrated for this molecule. Parallel-stacked aggregates, from dimers to higher-order aggregates, which are absent in the crystal, are found to be thermodynamically most favorable due to the presence of strong short-range C-H⋅⋅⋅F-C intermolecular hydrogen-bonding networks. Because of their cooperative nature, binding energies, dipole moments, and polarizations per molecule increase from monomer to tetramer, whereas the HOMO-LUMO gaps follow the opposite trend. Based on the DFT-D3 calculations, it is proposed that this parallel-stacked arrangement can be further extended to prepare stable a 1D crystal such that a large dipole moment and macroscopic polarizations can arise, which might be useful in designing electronic and nonlinear optical devices. Because the molecule has conformational flexibility, the potential energy surface is investigated for ring flipping and the effects of fluorine substitution are studied by comparing the barrier with respect to cyclohexane and all-cis-1,2,3-trifluorocyclohexane. PMID:27124861

  8. Interpreting human behavior from depositional rates and combustion features through the study of sedimentary microfacies at site Pinnacle Point 5-6, South Africa.

    PubMed

    Karkanas, Panagiotis; Brown, Kyle S; Fisher, Erich C; Jacobs, Zenobia; Marean, Curtis W

    2015-08-01

    Using fine and coarse resolution geoarchaeological studies at the Middle Stone Age site of PP5-6 at Pinnacle Point, Mossel Bay, South Africa, we discovered different patterns of anthropogenic input and changes in behavior through time. Through the microfacies approach, we documented the various geogenic and anthropogenic processes that formed the deposits of the site. By deciphering large scale rate differences in the production of these microfacies we estimated anthropogenic input rates and therefore gained understanding of occupational duration and intensity. The PP5-6 sediments document occupations characterized by small groups and short visits during Marine Isotope Stage (MIS) 5. This part of the sequence is characterized by numerous single (and mostly intact) hearth structures in a roofspall-rich matrix. During this time the sea was very close to the site and the people were focused on exploiting the rocky shores. With the advent of the glacial conditions of MIS4, the occupation of the site became much more intense. The occurrence of thick palimpsests of burnt remains, sometimes disturbed by small-scale sedimentary gravity processes, supports this conclusion. As sea level dropped and the coastline retreated, the geogenic input shifted to predominately aeolian sediments, implying an exposed shelf probably associated with a rich but more distant coastal environment. The occupants of PP5-6 turned their preference to silcrete as a raw material and they began to make microlithic stone tools. Since sites dating to MIS4 are abundant in the Cape, we suggest that populations during MIS4 responded to glacial conditions with either demographic stability or growth as well as technological change. PMID:26024567

  9. 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.

  10. 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

  11. Carriers for metal complexes on tumour cells: the effect of cyclodextrins vs CNTs on the model guest phenanthroline-5,6-dione trithiacyclononane ruthenium(II) chloride.

    PubMed

    Braga, Susana S; Marques, Joana; Heister, Elena; Diogo, Cátia V; Oliveira, Paulo J; Paz, Filipe A Almeida; Santos, Teresa M; Marques, Maria Paula M

    2014-06-01

    The complex [Ru[9]aneS3(pdon)Cl]Cl (pdon = 1,10-phenanthroline-5,6-dione) was readily obtained from the stoichiometric reaction of Ru[9]aneS3(dmso)Cl2 with pdon. Recrystallisation in ethanol using salicylic acid as a co-crystallisation helper afforded single-crystals suitable for the collection of X-ray diffraction data which afforded a reasonable structural description. Two different kinds of molecular carriers were tested as vehicles for this complex: carbon nanotubes (CNTs) and cyclodextrins. CNTs had an insufficient loading rate for the ruthenium complex at CNT concentrations deemed non-cytotoxic on cultured cells. The cyclodextrin (CD) carriers, β-CD and TRIMEB (standing for permethylated β-CD), were able to form two adducts, studied by powder X-ray diffraction, thermogravimetric analysis (TGA), (13)C{(1)H} CP/MAS NMR and FT-IR spectroscopies. The DNA thermal denaturation studies showed that the complex 1 is able to intercalate with DNA. The in vitro cytotoxicity of the free complex [Ru[9]aneS3(pdon)Cl]Cl (1) and of its two CD adducts (2 and 3) was assessed on both rodent and human cell lines. By using the mouse K1735-M2 melanoma cell line and the non-tumour rat H9c2 cardiomyoblasts, the results showed that 1 and 2 significantly inhibited the growth of the tumour cell line while displaying a good safety profile on cardiomyoblasts. Compound 3 at 100 μM inhibited the proliferation of both cell lines, with a higher activity towards the melanoma cell line. The cytotoxicity of the compounds 1-3 was further assessed on human breast cancer cell lines. Against the MDA-MB-231 line, growth inhibition occurred only with 1 and 3 at the incubation time of 96 h, both with approximate inhibition rates of 50 %; against the MCF-7 line, mild cytotoxicity was observed at 48 h of incubation, with IC50 values calculated above 100 μM for 1, 2 and 3. PMID:24652595

  12. 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. PMID:2343458

  13. Synthesis of S-(-)-5,6-Dihydrocanthin-4-ones via a Triple Cooperative Catalysis-Mediated Domino Reaction.

    PubMed

    Dighe, Shashikant U; Mahar, Rohit; Shukla, Sanjeev K; Kant, Ruchir; Srivastava, Kumkum; Batra, Sanjay

    2016-06-01

    An enantioselective synthesis of S-(-)-5,6-dihydrocanthin-4-ones via a triple cooperative catalysis-mediated domino reaction having a broad substrate scope is reported. The reaction between substituted 1-formyl-9H-β-carbolines and terminal alkynes in the presence of catalytic amounts of Jorgensen-Hayashi catalyst, copper iodide, and Hunig base proceeded via a multicascade route, affording the title compounds in good yields and excellent ees with interesting mechanistic features. These compounds were assessed for in vitro antiplasmodial activity against P. falciparum strains. Additionally, 5,6-dihydrocanthin-4-ones are demonstrated to be a versatile precursor to different fused β-carboline derivatives via simple synthetic transformations. PMID:27159615

  14. Polarization Components in π0 Photoproduction at Photon Energies up to 5.6 GeV

    NASA Astrophysics Data System (ADS)

    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.; 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.; Marsh, A.; Matulenko, Y.; Maxwell, J.; Mbianda, G.; 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.; Širca, 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.

    2012-06-01

    We present new data for the polarization observables of the final state proton in the H1(γ→,p→)π0 reaction. These data can be used to test predictions based on hadron helicity conservation and perturbative QCD. 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° in the center-of-mass frame. The data extend the polarization measurements database for neutral pion photoproduction up to Eγ=5.6GeV. The results show a nonzero 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 hadron helicity conservation does not hold and that the perturbative QCD limit is still not reached in the energy regime of this experiment.

  15. Antimalarial 5,6-Dihydro-α-pyrones from Cryptocarya rigidifolia: Related Bicyclic Tetrahydro-α-Pyrones Are Artifacts1

    PubMed Central

    2016-01-01

    Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A–E (1–5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F–K (6–11). The structure elucidations of all compounds were made on the basis of the interpretation of spectroscopic data and chemical derivatization, and the relative and absolute configurations were determined by NOESY, electronic circular dichroism (ECD), and 1H NMR analysis of α-methoxyphenylacetyl (MPA) derivatives. The bicyclic tetrahydro-α-pyrone derivatives were identified as products of acid-catalyzed intramolecular Michael addition of the 5,6-dihydro-α-pyrones in the presence of silica gel. A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity. PMID:26042470

  16. Euphorikanin A, a Diterpenoid Lactone with a Fused 5/6/7/3 Ring System from Euphorbia kansui.

    PubMed

    Fei, Dong-Qing; Dong, Le-Le; Qi, Feng-Ming; Fan, Gai-Xia; Li, Hui-Hong; Li, Zheng-Yu; Zhang, Zhan-Xin

    2016-06-17

    Euphorikanin A (1), an unprecedented diterpenoid lactone which possesses a novel 5/6/7/3-fused tetracyclic ring skeleton, was isolated from the roots of Euphorbia kansui. The chemical structure and absolute stereochemistry were elucidated on the basis of extensive spectroscopic methods and single-crystal X-ray diffraction analysis. Compound 1 exhibited moderate cytotoxicity against two human tumor cell lines HeLa and NCI-446. A proposed biosynthetic pathway of compound 1 is also described. PMID:27230557

  17. A Combined Experimental and Theoretical Approach to the Photogeneration of 5,6-Dihydropyrimidin-5-yl Radicals in Nonaqueous Media.

    PubMed

    Aparici-Espert, Isabel; Francés-Monerris, Antonio; Rodríguez-Muñiz, Gemma M; Roca-Sanjuán, Daniel; Lhiaubet-Vallet, Virginie; Miranda, Miguel A

    2016-05-20

    The chemical fate of radical intermediates is relevant to understand the biological effects of radiation and to explain formation of DNA lesions. A direct approach to selectively generate the putative reactive intermediates is based on the irradiation of photolabile precursors. But, to date, radical formation and reactivity have only been studied in aqueous media, which do not completely mimic the microenvironment provided by the DNA structure and its complexes with proteins. Thus, it is also important to evaluate the photogeneration of nucleoside-based radicals in nonaqueous media. The attention here is focused on the independent generation of 5,6-dihydropyrimidin-5-yl radicals in organic solvent through the synthesis of new lipophilic tert-butyl ketone precursors. Formation of 5,6-dihydro-2'-deoxyuridin-5-yl and 5,6-dihydrothymidin-5-yl radicals has first been confirmed by using a new nitroxide-derived profluorescent radical trap. Further evidence has been obtained by nanosecond laser flash photolysis through detection of long-lived transients. Finally, the experimental data are corroborated by multiconfigurational ab initio CASPT2//CASSCF methodology. PMID:27088245

  18. 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

  19. Third-order nonlinear optical investigations of meso-tetrakis(2,3,5,6-tetrafluoro-N,N-dimethyl-4-anilinyl)porphyrin and its metal complexes

    NASA Astrophysics Data System (ADS)

    Siji Narendran, N. K.; Soman, Rahul; Arunkumar, Chellaiah; Chandrasekharan, K.

    2015-02-01

    We report here the experimental investigation on third-order nonlinear optical parameters of 5,10,15,20-tetrakis(2,3,5,6-tetrafluoro-N,N-dimethyl-4-anilinyl)porphyrin and its various metal complexes, using Z-scan technique at 532 nm. The third-order nonlinear optical susceptibilities (χ(3)) were of the order 10-12 esu and are compared through degenerate four wave mixing (DFWM). The operating mechanism is reverse saturable absorption (RSA) as the effective excited-state absorption cross-section was found higher than ground state absorption cross-section as well as the magnitude of nonlinear absorption coefficient was found decreasing with on-axis input intensity. The compounds found to exhibit good optical limiting at 532 nm, 7 ns excitation steering applications in laser safety.

  20. Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase from Maize: Molecular and Biochemical Characterization[OA

    PubMed Central

    Sun, Yuejin; Thompson, Mark; Lin, Gaofeng; Butler, Holly; Gao, Zhifang; Thornburgh, Scott; Yau, Kerrm; Smith, Doug A.; Shukla, Vipula K.

    2007-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase, an enzyme encoded by the gene IPK1, catalyzes the terminal step in the phytic acid biosynthetic pathway. We report here the isolation and characterization of IPK1 cDNA and genomic clones from maize (Zea mays). DNA Southern-blot analysis revealed that ZmIPK1 in the maize genome constitutes a small gene family with two members. Two nearly identical ZmIPK1 paralogs, designated as ZmIPK1A and ZmIPK1B, were identified. The transcripts of ZmIPK1A were detected in various maize tissues, including leaves, silks, immature ears, seeds at 12 d after pollination, midstage endosperm, and maturing embryos. However, the transcripts of ZmIPK1B were exclusively detected in roots. A variety of alternative splicing products of ZmIPK1A were discovered in maize leaves and seeds. These products are derived from alternative acceptor sites, alternative donor sites, and retained introns in the transcripts. Consequently, up to 50% of the ZmIPK1A transcripts in maize seeds and leaves have an interrupted open reading frame. In contrast, only one type of splicing product of ZmIPK1B was detected in roots. When expressed in Escherichia coli and subsequently purified, the ZmIPK1 enzyme catalyzes the conversion of myo-inositol 1,3,4,5,6-pentakisphosphate to phytic acid. In addition, it is also capable of catalyzing the phosphorylation of myo-inositol 1,4,6-trisphosphate, myo-inositol 1,4,5,6-tetrakisphosphate, and myo-inositol 3,4,5,6-tetrakisphosphate. Nuclear magnetic resonance spectroscopy analysis indicates that the phosphorylation product of myo-inositol 1,4,6-trisphosphate is inositol 1,2,4,6-tetrakisphosphate. Kinetic studies showed that the Km for ZmIPK1 using myo-inositol 1,3,4,5,6-pentakisphosphate as a substrate is 119 μm with a Vmax at 625 nmol/min/mg. These data describing the tissue-specific accumulation and alternative splicing of the transcripts from two nearly identical ZmIPK1 paralogs suggest that maize has a highly sophisticated

  1. 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…

  2. Conformational and electronic properties of the two cis (5S,6R) and (5R,6S) diastereoisomers of 5,6-dihydroxy-5,6-dihydrothymidine: X-ray and theoretical studies.

    PubMed

    Jolibois, F; Voituriez, L; Grand, A; Cadet, J

    1996-01-01

    The structure of (+)-cis-(5S,6R)-5,6-dihydroxy-5,6-dihydrothymidine was obtained using X-ray crystallography [space group P2(1) with a = 10.130(3) angstroms, b = 6.434(9) angstroms, c = 11.02(5) angstroms, and beta = 112.646(2) angstroms]. The comparison of the two cis diastereoisomers of thymidine glycol (I, II) showed several structural and conformational differences. The solid state structures appear to be in agreement with the results of 1H NMR studies which were carried out in aqueous solution. Conformational and electronic properties of the ground state of the molecules I and II were obtained using ab initio LSD-DFT theory. Only slight differences between the crystal structure and the optimized geometry are observed for each of the two oxidized nucleosides. On the other hand, molecules I and II exhibit significant differences in their electronic properties. In particular, the dipole moment of (5S,6R)-thymidine glycol (I) is twice smaller than that of the (5R,6S) diastereoisomer (II). It is noteworthy that these differences in the electronic properties between the two compounds may be related to changes in the rotameric population around the C4'-C5' bond. The repartition of the electrostatic potential is different in the two compounds. These observations lead to a better understanding of the structural changes when the above lesions are included within a DNA molecule. PMID:8924607

  3. Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats

    PubMed Central

    Tapia, Edilia; Soto, Virgilia; Ortiz-Vega, Karla Mariana; Zarco-Márquez, Guillermo; Molina-Jijón, Eduardo; Cristóbal-García, Magdalena; Santamaría, José; García-Niño, Wylly Ramsés; Correa, Francisco; Zazueta, Cecilia; Pedraza-Chaverri, José

    2012-01-01

    Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8–10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes. PMID:22919438

  4. 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…

  5. Tacrolimus restores podocyte injury and stabilizes the expression of Cabin1 in 5/6 nephrectomized rats.

    PubMed

    Wen, Yueqiang; Liu, Lingling; Zhou, Peilan; Li, Huiyuan; Wang, Zebin; Zhang, Yajie; Liang, Jianbo

    2016-05-01

    Podocyte injury is a vital factor, which induces massive proteinuria. Studies have shown that tacrolimus (TAC) protected podocyte via stabilizing cytoskeleton. Our latest study indicates that calcineurin binding protein 1 (Cabin1) undergoes nuclear translocation during podocytes injury. Whether TAC targets on Cabin1 during podocyte injury is still not clear. This study establishes non-immunological proteinuric model. To observe the effect of the treatment of TAC on Cabin1 expression in 5/6 nephrectomized rats. Sprague-Dawley rats were injected with TAC (0.2 mg/kg/day) for 4-8 weeks after 5/6 nephrectomy. Then, rats were sacrificed in the eighth week after operation, renal tissues were processed for morphological studies under light and electrical microscope. Cabin1 expression and distribution were detected by western blot and indirect immunofluorescence staining. In 5/6 nephrectomized rats, urinary protein excretion reached 90.2 ± 30.1 mg/24 h, glomerular sclerosis index and tubulointerstitial fibrosis score were significantly increased, and widespread of podocyte foot processes fusion was found. Moreover, Cabin1 protein expression was markedly increased, and its distribution became much more obviously in podocytes nuclei. In TAC treated rats, urinary protein excretion significantly decreased (44.9 ± 22.5 mg/24 h), glomerular sclerosis and tubulointerstitial fibrosis were alleviated, and podocyte foot processes fusion was inhibited. Furthermore, TAC alleviated the increased protein expression and abnormal distribution of Cabin1. In conclusion, TAC restores podocyte injury and stabilizes the expression of Cabin1. Cabin1 may become a new target to demonstrate the mechanism of TAC in podocyte injury. PMID:26905810

  6. Phagraphene: A Low-Energy Graphene Allotrope Composed of 5-6-7 Carbon Rings with Distorted Dirac Cones.

    PubMed

    Wang, Zhenhai; Zhou, Xiang-Feng; Zhang, Xiaoming; Zhu, Qiang; Dong, Huafeng; Zhao, Mingwen; Oganov, Artem R

    2015-09-01

    Using systematic evolutionary structure searching we propose a new carbon allotrope, phagraphene [fæ'græfi:n], standing for penta-hexa-hepta-graphene, because the structure is composed of 5-6-7 carbon rings. This two-dimensional (2D) carbon structure is lower in energy than most of the predicted 2D carbon allotropes due to its sp(2)-binding features and density of atomic packing comparable to graphene. More interestingly, the electronic structure of phagraphene has distorted Dirac cones. The direction-dependent cones are further proved to be robust against external strain with tunable Fermi velocities. PMID:26262429

  7. Comparison of energy calibration of Prognoz 5, 6, 7, and 8 and other hard-X-ray solar photometers

    NASA Astrophysics Data System (ADS)

    Farnik, F.; Valnicek, B.; Sylwester, B.; Sylwester, J.; Jakimiec, J.

    1984-08-01

    The data obtained by the Prognoz 5, 6, 7, and 8 hard-X-ray photometers are compared with the measurements carried out by similar instruments aboard Solrad 11, ISEE 3, SMM, and Hinotori satellites. Using the method of relative-amplitude analysis, the apparent disagreement in the energy-discrimination-level calibration between the instruments is pointed out. The results of the comparison and possible sources of disagreement are given. An international effort to develop a system of uniform prelaunch calibration of photometers based on a reference calibration source is suggested.

  8. 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.

  9. 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…

  10. Design and syntheses of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione and N-(benzothiazol-5-yl)isoindoline-1,3-dione as potent protoporphyrinogen oxidase inhibitors.

    PubMed

    Jiang, Li-Li; Zuo, Yang; Wang, Zhi-Fang; Tan, Yin; Wu, Qiong-You; Xi, Zhen; Yang, Guang-Fu

    2011-06-01

    Discovery of protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors has been one of the hottest research areas in the field of herbicide development for many years. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-diones (1a-p) and N-(benzothiazol-5-yl)isoindoline-1,3-diones (2a-h) were designed and synthesized according to the ring-closing strategy of two ortho-substituents. The bioassay results indicated that some newly synthesized compounds exhibited higher PPO inhibition activity than the control of sulfentrazone. Compound 1a, S-(5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl) O-methyl carbonothioate, was identified as the most potent inhibitor with k(i) value of 0.08 μM, about 9 times higher than that of sulfentrazone (k(i) = 0.72 μM). Further green house assay showed that compound 1b, methyl 2-((5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)thio)acetate, exhibited herbicidal activity comparable to that of sulfentrazone even at a concentration of 37.5 g ai/ha. In addition, among six tested crops, wheat exhibited high tolerance to compound 1b even at a dosage of 300 g ai/ha. These results indicated that compound 1b might have the potential to be developed as a new herbicide for weed control of wheat field. PMID:21517076

  11. Synthesis, tumor inhibitory and antioxidant activity of new polyfunctionally 2-substituted 5,6,7,8-tetrahydronaphthalene derivatives containing pyridine, thioxopyridine and pyrazolopyridine moieties.

    PubMed

    Hamdy, Nehal A; Anwar, Manal M; Abu-Zied, Khadiga M; Awad, Hanem M

    2013-01-01

    2-Acetyl-5,6,7,8-tetrahydronaphthalene (1) was allowed to react with different aromatic aldehydes to produce the cyanopyridones 2a and 2b, which were treated with phosphorous pentasulfide to afford the corresponding thioxopyridine derivatives 3a and 3b, respectively. The reaction of 3a and 3b with ethyl bromoacetate afforded the ester derivatives 4a and 4b, while their condensation with hydrazine hydrate gave the corresponding pyrazolopyridine derivatives 5a and 5b. The reaction of the precursor 2-amino-5,6,7,8-tetrahydronaphthalene (6) with ethoxy methylenemalonic ester led to the formation of aminomethylenemalonate derivative 7. Cyclization of 7 in boiling diphenyl ether gave the derivative - ethyl 6,7,8,9-tetrahydro-4-hydroxybenzo[g]-quinoline-3-carboxylate (8) which was hydrolyzed to produce the corresponding carboxylic acid analogue 9. Further reaction of 3a with 3-chloropropane-1,2-diol and/or iodomethane produced the corresponding nicotinonitrile derivatives 10 and 11. Hydrazinolysis of derivative 11 gave the hydrazinyl derivative 12. Moreover, chlorination of compound 2a with phosphorous oxychloride led to 2-chloro nicotinonitrile derivative 13, which was refluxed with various amines to form the corresponding derivatives 5a, 14 and 15. Treatment of the pyrazolopyridine compound 5a with formic acid and acetic anhydride afforded the corresponding formamide and acetamide analogues 16 and 17, while its reaction with DMF-DMA yielded the corresponding formimidamide derivative 18. The pyridopyrazolo[1,5-a]pyrimidine derivative 19 was obtained by cyclization of 5a with acetyl acetone. The antioxidant activity evaluation of the newly synthesized compounds showed that the pyrazolopyridine derivative 5a exhibited scavenging potency higher than that obtained by ascorbic acid. Tumor inhibitory activity screening revealed that derivatives 8 and 10 showed promising potency against the liver cancer cells (HepG-2) compared to doxorubicin as a reference drug. PMID:24383322

  12. Estimation of doses to Taikonauts in SZ-5/6/7 missions using a male voxel model

    NASA Astrophysics Data System (ADS)

    Xu, Feng; Zeng, Zhi; Jia, Xianghong

    2011-11-01

    Objective To assess the Taikonaut's space radiation risk organ, doses have been calculated using a male voxel model. Methods A male voxel model based on MRI was built. The proton spectra were calculated by AP-8 with SPENVIS and Badhwar's GCR model. The general 3 D Monte Carlo particle and heavy ion transport code GEANT4 was used to calculate the average doses for some organs and tissues. Results After 1 g/cm2 shielding shell, the absorbed dose rate of skin is 0.6 mGy/d and effective dose rate is estimated to be 2.3 mSv/d during the SZ-5/6/7 mission. The total effective dosesof the taikonauts are estimated to be around 2.0 mSv during the SZ-5 mission, 10.9mSv during the SZ-6 mission and 6.5 mSv during the SZ-7 mission separately. Conclusion The calculated skin doses are closed to the values measured by TLDs in SZ-5/6/7, and within the range of 0.2~0.6mSv published by USA and Russia.

  13. Estimation of doses to Taikonauts in SZ-5/6/7 missions using a male voxel model

    NASA Astrophysics Data System (ADS)

    Xu, Feng; Zeng, Zhi; Jia, Xianghong

    2012-03-01

    Objective To assess the Taikonaut's space radiation risk organ, doses have been calculated using a male voxel model. Methods A male voxel model based on MRI was built. The proton spectra were calculated by AP-8 with SPENVIS and Badhwar's GCR model. The general 3 D Monte Carlo particle and heavy ion transport code GEANT4 was used to calculate the average doses for some organs and tissues. Results After 1 g/cm2 shielding shell, the absorbed dose rate of skin is 0.6 mGy/d and effective dose rate is estimated to be 2.3 mSv/d during the SZ-5/6/7 mission. The total effective dosesof the taikonauts are estimated to be around 2.0 mSv during the SZ-5 mission, 10.9mSv during the SZ-6 mission and 6.5 mSv during the SZ-7 mission separately. Conclusion The calculated skin doses are closed to the values measured by TLDs in SZ-5/6/7, and within the range of 0.2~0.6mSv published by USA and Russia.

  14. 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.

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

    DOE PAGESBeta

    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.; et al

    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

  16. 5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

    PubMed

    Kumagai, Momochika; Mishima, Takashi; Watanabe, Akio; Harada, Teppei; Yoshida, Izumi; Fujita, Kazuhiro; Watai, Masatoshi; Tawata, Shinkichi; Nishikawa, Keisuke; Morimoto, Yoshiki

    2016-07-01

    Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent. PMID:26940726

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

    PubMed

    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; 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; Marsh, A; Matulenko, Y; Maxwell, J; Mbianda, G; 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; Širca, 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

    2012-06-01

    We present new data for the polarization observables of the final state proton in the (1)H(γ,p)π(0) reaction. These data can be used to test predictions based on hadron helicity conservation and perturbative QCD. These data have both small statistical and systematic uncertainties and were obtained with beam energies between 1.8 and 5.6 GeV and for π(0) scattering angles larger than 75° in the center-of-mass frame. The data extend the polarization measurements database for neutral pion photoproduction up to E(γ)=5.6 GeV. The results show a nonzero induced polarization above the resonance region. The polarization transfer components vary rapidly with the photon energy and π(0) scattering angle in the center-of-mass frame. This indicates that hadron helicity conservation does not hold and that the perturbative QCD limit is still not reached in the energy regime of this experiment. PMID:23180491

  18. Evaluation of a color-coded Landsat 5/6 ratio image for mapping lithologic differences in western South Dakota

    USGS Publications Warehouse

    Raines, Gary L.; Bretz, R.F.; Shurr, George W.

    1979-01-01

    From analysis of a color-coded Landsat 5/6 ratio, image, a map of the vegetation density distribution has been produced by Raines of 25,000 sq km of western South Dakota. This 5/6 ratio image is produced digitally calculating the ratios of the bands 5 and 6 of the Landsat data and then color coding these ratios in an image. Bretz and Shurr compared this vegetation density map with published and unpublished data primarily of the U.S. Geological Survey and the South Dakota Geological Survey; good correspondence is seen between this map and existing geologic maps, especially with the soils map. We believe that this Landsat ratio image can be used as a tool to refine existing maps of surficial geology and bedrock, where bedrock is exposed, and to improve mapping accuracy in areas of poor exposure common in South Dakota. In addition, this type of image could be a useful, additional tool in mapping areas that are unmapped.

  19. Polarization of the strongest nf→3d (n = 4, 5, 6) radiative lines emitted from tungsten ions following EIE and DR processes

    NASA Astrophysics Data System (ADS)

    Ma, X. Y.; Wu, Z. W.; Dong, C. Z.; Shi, Y. L.; Xie, L. Y.

    2014-04-01

    Electron-impact excitation and resonant electron capture cross sections to the specific magnetic sublevels of highly charged Ni-like to Ge-like tungsten ions have been calculated systematically by using a fully relativistic distorted-wave method. And these magnetic cross sections have further been employed to obtain the degrees of linear polarization of the corresponding strongest nf → 3d (n = 4, 5, 6) x-rays. We compare polarizations of the same lines but from the above two different processes for the first time. It has been found the polarizations following both the both processes are totally different. It is expected that the obvious differences between the polarizations can be used to distinguish the formation mechanism of the corresponding lines.

  20. Biochemical and Structural Studies of 6-Carboxy-5,6,7,8-tetrahydropterin Synthase Reveal the Molecular Basis of Catalytic Promiscuity within the Tunnel-fold Superfamily*

    PubMed Central

    Miles, Zachary D.; Roberts, Sue A.; McCarty, Reid M.; Bandarian, Vahe

    2014-01-01

    6-Pyruvoyltetrahydropterin synthase (PTPS) homologs in both mammals and bacteria catalyze distinct reactions using the same 7,8-dihydroneopterin triphosphate substrate. The mammalian enzyme converts 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin, whereas the bacterial enzyme catalyzes the formation of 6-carboxy-5,6,7,8-tetrahydropterin. To understand the basis for the differential activities we determined the crystal structure of a bacterial PTPS homolog in the presence and absence of various ligands. Comparison to mammalian structures revealed that although the active sites are nearly structurally identical, the bacterial enzyme houses a His/Asp dyad that is absent from the mammalian protein. Steady state and time-resolved kinetic analysis of the reaction catalyzed by the bacterial homolog revealed that these residues are responsible for the catalytic divergence. This study demonstrates how small variations in the active site can lead to the emergence of new functions in existing protein folds. PMID:24990950

  1. 40 CFR 721.9504 - Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8-tridecafluorooctyl)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Silane, triethoxy (3,3,4,4,5,5, 6,6,7... Significant New Uses for Specific Chemical Substances § 721.9504 Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8... substance identified as silane, triethoxy (3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)- (PMN...

  2. 40 CFR 721.9504 - Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8-tridecafluorooctyl)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Silane, triethoxy (3,3,4,4,5,5, 6,6,7... Significant New Uses for Specific Chemical Substances § 721.9504 Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8... substance identified as silane, triethoxy (3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)- (PMN...

  3. 40 CFR 721.9504 - Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8-tridecafluorooctyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Silane, triethoxy (3,3,4,4,5,5, 6,6,7... Significant New Uses for Specific Chemical Substances § 721.9504 Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8... substance identified as silane, triethoxy (3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)- (PMN...

  4. 40 CFR 721.9504 - Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8-tridecafluorooctyl)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Silane, triethoxy (3,3,4,4,5,5, 6,6,7... Significant New Uses for Specific Chemical Substances § 721.9504 Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8... substance identified as silane, triethoxy (3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)- (PMN...

  5. 40 CFR 721.9504 - Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8-tridecafluorooctyl)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Silane, triethoxy (3,3,4,4,5,5, 6,6,7... Significant New Uses for Specific Chemical Substances § 721.9504 Silane, triethoxy (3,3,4,4,5,5, 6,6,7,7,8,8,8... substance identified as silane, triethoxy (3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)- (PMN...

  6. 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

  7. On the contribution of stereochemistry to human ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrate.

    PubMed

    Riley, Andrew M; Deleu, Sandrine; Qian, Xun; Mitchell, Jennifer; Chung, Sung-Kee; Adelt, Stephan; Vogel, Günter; Potter, Barry V L; Shears, Stephen B

    2006-01-01

    Ins(1,4,5,6)P4, a biologically active cell constituent, was recently advocated as a substrate of human Ins(3,4,5,6)P4 1-kinase (hITPK1), because stereochemical factors were believed relatively unimportant to specificity [Miller, G.J., Wilson, M.P., Majerus, P.W. and Hurley, J.H. (2005) Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-triphosphate 5/6-kinase. Mol. Cell. 18, 201-212]. Contrarily, we provide three examples of hITPK1 stereospecificity. hITPK1 phosphorylates only the 1-hydroxyl of both Ins(3,5,6)P3 and the meso-compound, Ins(4,5,6)P3. Moreover, hITPK1 has >13,000-fold preference for Ins(3,4,5,6)P4 over its enantiomer, Ins(1,4,5,6)P4. The biological significance of hITPK1 being stereospecific, and not physiologically phosphorylating Ins(1,4,5,6)P4, is reinforced by our demonstrating that Ins(1,4,5,6)P4 is phosphorylated (K(m) = 0.18 microM) by inositolphosphate-multikinase. PMID:16376887

  8. Stride time variability as a marker for higher level of gait control in multiple sclerosis: its association with fear of falling.

    PubMed

    Allali, Gilles; Laidet, Magali; Armand, Stéphane; Elsworth-Edelsten, Charlotte; Assal, Frédéric; Lalive, Patrice H

    2016-06-01

    Fear of falling (FOF) and gait disorders represent both prevalent symptoms in patients with multiple sclerosis (MS); however, the association between FOF and higher level of gait control (HLGC) has not been studied in MS. This study aims to assess the association between FOF and HLGC in patients with MS. HLGC was assessed by stride time variability (STV) during single and dual-tasks (forward counting, backward counting, categorical verbal fluency and literal verbal fluency) and FOF was quantified by the falls efficacy scale-international (FES-I). Seventy-one patients (age: 39.27 ± 9.77 years; 63 % female) were included in this cross-sectional study (Expanded Disability Status Scale (median): 2.00) with a low prevalence of FOF (FES-I: 21.52 ± 8.37). The mean gait speed was 1.19 ± 0.23 m/s with a STV of 2.35 ± 1.68 % during single walking task. STV during single task and the dual tasks of forward counting and backward counting were associated with the FES-I in the univariable linear regression models (p ≤ 0.001), but only STV while backward counting (β: 0.42, [0.18;0.66]) was associated with FOF in the multivariable model (adjusted for age, gender, previous fall, Expanded Disability Status Scale and gait speed). These findings indicate that FOF is associated with STV while backward counting, a marker of HLGC in relationship with working memory in a MS population including a majority of low disabled patients. PMID:27106906

  9. Time?

    NASA Astrophysics Data System (ADS)

    Amoroso, Richard L.

    2013-09-01

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

  10. 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.

  11. From Lean Times to Enrollment Declines: The Governor's Commission on the Future of Higher Education in Michigan. ASHE Annual Meeting Paper.

    ERIC Educational Resources Information Center

    Widmayer, Patricia

    Conditions in higher education in Michigan and the role of the Governor's Commission on the Future of Higher Education in Michigan are highlighted. The average college tuition rate in Michigan is the highest in the nation, and a critical maintenance and equipment problem exists. The Commission is composed of knowledgeable persons without vested…

  12. 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…

  13. 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)…

  14. 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…

  15. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    This eighth chapter of "The Yearbook of School Law, 1986" summarizes and analyzes over 330 state and federal court cases litigated in 1985 in which institutions of higher education were involved. Among the topics examined were relationships between postsecondary institutions and various governmental agencies; discrimination in the employment of…

  16. The stereochemical outcome of electrophilic addition reactions on the 5,6-double bond in the spinosyns.

    PubMed

    De Amicis, C V; Graupner, P R; Erickson, J A; Paschal, J W; Kirst, H A; Creemer, L C; Fanwick, P E

    2001-12-14

    The electrophilic addition of reagents to the 5,6-double bond in spinosyn A and spinosyn D systems occurred with high pi-diastereofacial selectivity. Addition occurred preferentially from the beta face of the molecule with selectivities ranging from 5:1 to better than 30:1. Various NMR properties were investigated in order to distinguish the beta and alpha isomers with the help of theoretical models of the products. These NMR properties include a (13)C gamma effect to C-11 and vicinal coupling between H-4 and H-5. To help rationalize the selectivity, computational studies on the transition states for epoxidation were calculated using density functional theory. The results indicate that beta epoxidation is favored and that the geometries of the transition structures are consistent with torsional steering being the source of the selectivity. PMID:11735521

  17. Flexible charge balanced stimulator with 5.6 fC accuracy for 140 nC injections.

    PubMed

    Nag, Sudip; Jia, Xiaofeng; Thakor, Nitish V; Sharma, Dinesh

    2013-06-01

    Electrical stimulations of neuronal structures must ensure net injected charges to be zero for biological safety and voltage compliance reasons. We present a novel architecture of general purpose biphasic constant current stimulator that exhibits less than 5.6 fC error while injecting 140 nC charges using 1.4 mA currents. The floating current sources and conveyor switch based system can operate in monopolar or bipolar modes. Anodic-first or cathodic-first pulses with optional inter-phase delays have been demonstrated with zero quiescent current requirements at the analog front-end. The architecture eliminates blocking capacitors, electrode shorting and complex feedbacks. Bench-top and in-vivo measurement results have been presented with emulated electrode impedances (resistor-capacitor network), Ag-AgCl electrodes in saline and in-vivo (acute) peripheral nerve stimulations in anesthetized rats. PMID:23853326

  18. Synthesis of 1,4,5,6-tetrahydropyridine derivatives starting from trans-3-chloro-1,3-alkadien-5-ones

    SciTech Connect

    Melikyan, G.G.; Atanesyan, K.A.; Aslanyan, G.Kh.; Tirakyan, M.R.; Khachatryan, L.A.; Badanyan, Sh.O.

    1987-10-01

    A method has been developed for the synthesis of 3-carbethoxy-2-methyl-6-(oxo-alkylidene)-1,4,5,6-tetrahydropyridines by reaction of trans-3-chloro-1,3-alkadien-5-ones with ethyl aminocrotonate. It is shown that the corresponding vinylacetylanic ketones are intermediate products of the reactions. PMR spectra in CCl/sub 4/ were obtained on a Perkin-Elmer R12B (60 MHz) spectrometer, with TMS as internal standard. /sup 13/C NMR spectra were recordeed on a Bruker WH-90 instrument (22.63 MHz) without suppression and with complete suppression of spin-spin coupling. IR spectra were recorded in CCl/sub 4/ on a UR-10 instrument, mass spectra were recorded on a MX-1303 spectrometer with electron ionization energy of 30 eV.

  19. 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)).

  20. New 2-phenyl-4,5,6,7-tetrahydro-2H-indazole derivatives as paddy field herbicides.

    PubMed

    Hwang, In Taek; Kim, Hyoung Rae; Jeon, Dong Ju; Hong, Kyung Sik; Song, Jong Hwan; Chung, Chang Kook; Cho, Kwang Yun

    2005-05-01

    A series of 3-chloro-2-(4-chloro-2-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole derivatives containing various substituted isoxazolinylmethoxy groups at the 5-position of the benzene ring were synthesized and their herbicidal activities assessed under greenhouse and flooded paddy conditions. Among them, compounds having a phenyl or cyano substituent at the 3-position of the 5-methyl-isoxazolin-5-yl structure demonstrated good rice selectivity and potent herbicidal activity against annual weeds at 16-63 g AI ha(-1) under greenhouse conditions. Field trials indicated that these two compounds controlled a wide range of annual weeds rapidly with a good tolerance on transplanted rice seedlings by pre-emergence application. They showed a low mammalian and environmental toxicity in various toxicological tests. PMID:15627239

  1. 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.

  2. Design, Synthesis and Evaluation of Novel 2,5,6-Trisubstituted Benzimidazoles Targeting FtsZ as Antitubercular Agents

    PubMed Central

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

    2014-01-01

    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. PMID:24726304

  3. Spark-Plasma Sintering of W-5.6Ni-1.4Fe Heavy Alloys: Densification and Grain Growth

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    W-5.6Ni-1.4Fe heavy alloys were prepared by the method of spark-plasma sintering, and the densification and grain growth kinetics were analyzed as a function of various parameters such as sintering temperature and dwell duration. It is found that the local temperature gradient at the vicinity of the pores can cause the matrix phase melting or softening, resulting in a viscous layer coating the W particles and an improved solubility of W into the matrix phase. In the initial stage, particle rearrangement and neck formation and growth take place, and γ-(Ni, Fe) matrix phase has formed. Dissolution-precipitation and Ni-enhanced W grain boundary diffusion together with viscous process contribute to the simultaneous densification and grain growth in the intermediate stage. During the final stage, fast grain growth, controlled by both gas-phase diffusion and dissolution-precipitation mechanisms, dominates over the densification.

  4. Spectrofluorimetric determination of nitric oxide at trace levels with 5,6-diamino-1,3-naphthalene disulfonic acid.

    PubMed

    Zhang, Xian; Wang, Hong; Liang, Shu-Cai; Zhang, Hua-Shan

    2002-03-01

    Based on the selective reaction that 5,6-diamino-1,3-naphthalene disulfonic acid (DANDS) traps nitric oxide (NO) in the presence of dioxygen to yield the highly fluorescent form, 1-[H]-naphthotriazole-6,8-disulfonic acid in moderately alkaline medium, a new spectrofluorimetric method for the determination of NO has been reported. The method offered the advantage of specificity, sensitivity and a simple protocol for the direct detection of NO in aqueous solution. The linear calibration range for NO was 0.04-1.44 mumoll(-1) with a 3sigma detection limit of 0.6 nmoll(-1). The proposed method has been used to monitor the release of NO from S-nitrosocysteine, a NO-releasing agent. PMID:18968522

  5. Structure-based discovery of novel 4,5,6-trisubstituted pyrimidines as potent covalent Bruton's tyrosine kinase inhibitors.

    PubMed

    Zou, Yi; Xiao, Jianhu; Tu, Zhengchao; Zhang, Yingyi; Yao, Kun; Luo, Minghao; Ding, Ke; Zhang, Yihua; Lai, Yisheng

    2016-07-01

    A series of novel 4,5,6-trisubstituted pyrimidines were designed as potent covalent Bruton's tyrosine kinase (BTK) inhibitors based on the structure of ibrutinib by using a ring-opening strategy. Among these derivatives, compound I1 exhibited the most potent inhibitory activity with an IC50 value of 0.07μM. The preliminary structure-activity relationship was discussed and the primary amino group at the C-4 position of pyrimidine was crucial for maintaining BTK activity. Furthermore, molecular dynamics simulations and binding free energy calculations were performed for three inhibitor-BTK complexes to determine the probable binding model, which provided a comprehensive guide for further structural modification and optimization. PMID:27210433

  6. Synthesis and antinociceptive activity of new 2-substituted 4-(trifluoromethyl)-5,6-dihydrobenzo[h]quinazolines.

    PubMed

    Bonacorso, Helio G; Rosa, Wilian C; Oliveira, Sara M; Brusco, Indiara; Pozza, Camila C Dalla; Nogara, Pablo A; Wiethan, Carson W; Rodrigues, Melissa B; Frizzo, Clarissa P; Zanatta, Nilo

    2016-10-01

    A useful synthetic route for an initial new series of 2-substituted 4-(trifluoromethyl)-5,6-dihydrobenzo[h]quinazolines (3), as well as an evaluation of their analgesic effect in a mice pain model, is reported. Five new quinazolines were formed from the cyclocondensation reactions of 2,2,2-trifluoro-1-(1-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)ethanone (1) with some well-known amidine salts [NH2CR(=NH)] (2), in which R=H, Me, Ph, NH2 and SMe, at a 40-70% yield. Subsequently, due to the importance of the pyrrole nucleus, a 2-(pyrrol-1-yl)quinazoline (4) was obtained through a Clauson-Kaas reaction from the respective 2-(amino)quinazoline, in a reaction with 2,5-dimethoxy-tetrahydrofuran. The analgesic evaluation demonstrated that four 5,6-dihydrobenzo[h]quinazolines (compounds of 3c (R=Ph), 3d (R=NH2), 3e (R=SMe), and 4 (R=pyrrol-1-yl); 100mg/kg, p.o.) and ketoprofen (100mg/kg, p.o.) significantly reduced the spontaneous nociception in a capsaicin-induced test. Moreover, in comparison with ketoprofen (100 and 300mg/kg, p.o.), compound 3c (30-300mg/kg, p.o.) showed an anti-hyperalgesic action in an arthritic pain model without locomotor alterations in the mice, suggesting that quinazoline 3c is a promising prototype scaffold for new analgesic drugs in the treatment of pathological pain such as that in arthritis. PMID:27561714

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

    PubMed

    Ito, S; Nicol, J A

    1974-10-01

    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

  8. Synthesis and characterization of p-type conductivity dopant 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane

    SciTech Connect

    Rainbolt, James E.; Koech, Phillip K.; Polikarpov, Evgueni; Swensen, James S.; Cosimbescu, Lelia; Von Ruden, Amber L.; Wang, Liang; Sapochak, Linda S.; Padmaperuma, Asanga B.; Gaspar, Daniel J.

    2013-01-22

    We report the synthesis and characterization of 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane (F3TCNQ-Ad1), a substituted analog of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), designed for p-type conductivity doping. The dopant is designed as a model for substituted alternatives to F4TCNQ that maintain similar electronic properties with the goal of engineering dopants with superior fabrication characteristics over F4TCNQ. We describe the design strategy for F3TCNQ-Ad1 based on molecular modeling predictions that substitution of a single fluorine atom of F4TCNQ has little effect on the electronic properties of the molecule. Photophysical and electrochemical characterization reveal that the adamantyl substituent in F3TCNQ-Ad1 does not significantly alter the electronic properties of the substituted dopant relative to F4TCNQ. Unfortunately, F3TCNQ-Ad1 degrades under standard sublimation conditions, preventing sublimation deposition processing. Instead, hole-only devices were made via solution-processing of the p-doped films with the structure glass/ITO/2.3 x103Å PVK:(MTDATA:dopant)/2.0x102Å Au/1.0x103Å Al, where dopant is either F4TCNQ or F3TCNQ-Ad1. We demonstrate that F3TCNQ-Ad1 increased the conductivity of the films by at least 1,000 times compared to an undoped device.

  9. Syntheses of vanadyl and zinc(II) complexes of 1-hydroxy-4,5,6-substituted 2(1H)-pyrimidinones and their insulin-mimetic activities.

    PubMed

    Yamaguchi, Mika; Wakasugi, Kei; Saito, Ryota; Adachi, Yusuke; Yoshikawa, Yutaka; Sakurai, Hiromu; Katoh, Akira

    2006-02-01

    Control of the glucose level in the blood plasma has been achieved in vitro and in vivo by administration of vanadium and zinc in form of inorganic salts. It has been shown that elements are poorly absorbed in their inorganic forms and required high doses which have been associated with undesirable side effects. Many researchers, therefore, have focused on metal complexes that were prepared from VOSO(4) or ZnSO(4) and low-molecular-weight bidentate ligands. Seven kinds of 1-hydroxy-4,6-disubstituted and 1-hydroxy-4,5,6-trisubstituted-2(1H)-pyrimidinones were synthesized by reaction of N-benzyloxyurea and beta-diketones and subsequent removal of the protecting group. Six kinds of 1-hydroxy-4-(substituted)amino-2(1H)-pyrimidinones were synthesized by the substitution reaction of 1-benzyloxy-4-(1',2',4'-triazol-1'-yl)-2(1H)-pyrimidinone with various alkyl amines or amino acids. Treatment with VOSO(4) and ZnSO(4) or Zn(OAc)(2) afforded vanadyl(IV) and zinc(II) complexes which were characterized by means of (1)H NMR, IR, EPR, and UV-vis spectroscopies, and combustion analysis. The in vitro insulin-mimetic activity of these complexes was evaluated from 50% inhibitory concentrations (IC(50)) on free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. Vanadyl complexes of 4,6-disubstituted-2(1H)-pyrimidinones showed higher insulin-mimetic activities than those of 4,5,6-trisubstituted ones. On the other hand, Zn(II) complexes showed lower insulin-mimetic activities than VOSO(4) and ZnSO(4) as positive controls. It was found that the balance of the hydrophilicity and/or hydrophobicity is important for higher insulin-mimetic activity. The in vivo insulin-mimetic activity was evaluated with streptozotocin (STZ)-induced diabetic rats. Blood glucose levels were lowered from hyperglycemic to normal levels after the treatment with bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)oxovanadium(IV) by daily intraperitoneal injections. The improvement in

  10. Practical immunochemical method for determination of 3,5, 6-trichloro-2-pyridinol in human urine: applications and considerations for exposure assessment.

    PubMed

    Shackelford, D D; Young, D L; Mihaliak, C A; Shurdut, B A; Itak, J A

    1999-01-01

    An analytical method is described for the quantitative determination of 3,5,6-trichloro-2-pyridinol (3,5,6-TCP) in human urine. This is the primary analyte found in urine as a result of exposure to chlorpyrifos, chlorpyrifos-methyl, triclopyr, or 3,5,6-TCP. Conjugates of 3,5,6-TCP are released from urine by acid hydrolysis. The free 3,5,6-TCP is purified using C(18) solid-phase extraction, eluting the analyte with 1-chlorobutane. An aliquot of 1-chlorobutane is placed in a vial containing Trichloropyridinol Sample Diluent and evaporated, leaving the 3,5,6-TCP in the aqueous sample diluent. The samples are assayed using the Trichloropyridinol RaPID Assay immunoassay test kit. Final results are calculated using a standard curve constructed by linear regression after a ln/Logit data transformation is performed of the concentration and the absorbance readings, respectively. The calculated lower limit of quantitation for 3,5,6-TCP in fortified control urine samples is 2. 96 ng/mL (2.96 ppb). Residues of 3,5,6-TCP determined using both immunochemical and gas chromatography with mass spectrometric detection correlate well. PMID:10563869

  11. 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. ...

  12. Trivalent actinide and lanthanide complexation of 5,6-dialkyl-2,6-bis(1,2,4-triazin-3-yl)pyridine (RBTP; R = H, Me, Et) derivatives: a combined experimental and first-principles study.

    PubMed

    Bhattacharyya, Arunasis; Kim, Eunja; Weck, Philippe F; Forster, Paul M; Czerwinski, Kenneth R

    2013-01-18

    Complexations of lanthanide ions with 5,6-dialkyl-2,6-bis(1,2,4-triazin-3-yl)pyridine [RBTP; R = H (HBTP), methyl (MeBTP), ethyl (EtBTP)] derivatives have been studied in the acetonitrile medium by electrospray ionization mass spectrometry, time-resolved laser-induced fluorescence spectroscopy, and UV-vis spectrophotometric titration. These studies were carried out in the absence and presence of a nitrate ion in order to understand the effect of the nitrate ion on their complexation behavior, particularly in the poor solvating acetonitrile medium where strong nitrate complexation of hard lanthanide ions is expected. Consistent results from all three techniques undoubtedly show the formation of lower stoichiometric complexes in the presence of excess nitrate ion. This kind of nitrate ion effect on the speciation of Ln(3+) complexes of RBTP ligands has not so far been reported in the literature. Different Am(3+) and Ln(3+) complexes were observed with RBTP ligands in the presence of 0.01 M tetramethylammonium nitrate, and their stability constant values are determined using UV-vis spectrophotometric titrations. The formation of higher stoichiometric complexes and higher stability constants for Am(3+) compared to Ln(3+) ions indicates the selectivity of these classes of ligands. A single-crystal X-ray diffraction (XRD) study of europium(III) complexes shows the formation of a dimeric complex with HBTP and a monomeric complex with EtBTP, whereas MeBTP forms both the dimeric and monomeric complexes. Density functional theory calculations confirm the findings from single-crystal XRD and also predict the structures of Eu(3+) and Am(3+) complexes observed experimentally. PMID:23270453

  13. Two different deglaciation processes in the subtropical Pacific at MIS 5/6 and 1/2

    NASA Astrophysics Data System (ADS)

    Ujiie, Y.; Asahi, H.

    2011-12-01

    Deglaciation process is one of the results that the tropical climate forcing impact on the global changes by its large heat capacity. However, the deglacial fluctuation has poorly been explored in the tropical Pacific area due to less resolution records from the marine deposits. The Okinawa region is available to represent the high-resolution paleocenographic records of the tropical-subtropical Pacific during the late Quaternary, because of the oscillation between the Kuroshio Current continuing from the North Equatorial Current and central water of the subtropical gyre in this region. Two IMAGES cores were collected from the Okinawa Trough (under the Kuroshio Current) and Ryukyu Trench (under the central water of the subtropical gyre), respectively. Both cores MD982196 (Okinawa Trough) and MD012398 (Ryukyu Trench) covered over the records until Marine Isotope Stage (MIS) 7. Here, we aim to demonstrate the deglacial fluctuations of the surface and intermediate waters during two glacial-interglacial shifts, MIS 6 to 5 and MIS 2 to 1, based on the comprehensive analyses of the oxygen isotopes, Mg/Ca ratios of two planktic foraminiferal faunas (surface and upper intermediate species), and faunal assemblages of planktic foraminifera. The glacial-interglacial cycles were clearly confirmed in whole of the Okinawa region by the planktic δ18O curves. Surface Mg/Ca paleo-temperature showed a same trend as the δ18O curve. However, the paleo-temperature of the upper intermediate water showed unique fluctuation: temperature increased from late MIS 6 to 5e, whereas decreased from MIS 2 to Holocene. Moreover, the temperature difference (dT) between the surface and intermediate layers defined these phenomena. Fast warming of intermediate layer proitor to the deglaciation MIS 5/6 delayed a stratification of water column, while cooling of this layer make a large dT during MIS 1/2. Intriguingly, the faunal compositions of planktic foraminifera changed through the shifts of the

  14. 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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  15. 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. PMID:24878435

  16. Understanding the Changing Faculty Workforce in Higher Education: A Comparison of Full-Time Non-Tenure Track and Tenure Line Experiences

    ERIC Educational Resources Information Center

    Ott, Molly; Cisneros, Jesus

    2015-01-01

    Non-tenure track faculty are a growing majority in American higher education, but research examining their work lives is limited. Moreover, the theoretical frameworks commonly used by scholars have been critiqued for reliance on ideologically charged assumptions. Using a conceptual model developed from Hackman and Oldham's (1980) Job…

  17. 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…

  18. 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…

  19. 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…

  20. The 5-6 December 1991 FIRE IFO II jet stream cirrus case study: Possible influences of volcanic aerosols

    SciTech Connect

    Sassen, K.; Starr, D.O.C.; Melfi, S.H.; Spinhirne, J.D.; Poellot, M.R.; Eberhard, W.L.; Eloranta, E.W.; Hagen, D.E.; Hallett, J.

    1995-01-01

    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 Project FIRE IFO II 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 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 {minus}1}), complex radial ice crystal types, and relatively large haze particles in cirrus uncinus cell heads at temperatures between {minus}40{degrees} and {minus}50{degrees}C. Implications for volcanic-cirrus cloud climate effects and usual (nonvolcanic aerosol) jet stream cirrus cloud formation are discussed. 42 refs., 25 figs., 3 tabs.

  1. Determination of irradiation histories of raw beef livers using liquid chromatography-tandem mass spectrometry of 5,6-dihydrothymidine.

    PubMed

    Fukui, Naoki; Takatori, Satoshi; Kitagawa, Yoko; Okihashi, Masahiro; Ishikawa, Etsuko; Fujiyama, Takatomo; Kajimura, Keiji; Furuta, Masakazu; Obana, Hirotaka

    2017-02-01

    A method for detecting irradiation histories of raw beef livers was developed by measuring 5,6-dihydrothymidine (DHdThd) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Liver DNA was extracted using phenol-chloroform extraction followed by precipitation in 50% ethanol. DNA was then enzymatically digested and nucleosides were purified using an OASIS MCX column. DHdThd and thymidine (dThd) contents of resulting test solutions were analyzed using LC-MS/MS. DHdThd was detected specifically after γ-irradiation. Concentration ratios of DHdThd to dThd in the test solutions increased dose-dependently after irradiation at 1.0-11.3kGy, which included the practical dose for sterilization of 2-7kGy. Dose-response curves from beef livers of individual animals almost overlapped. Thus, this method is a candidate for the detection of irradiation histories of foods from which DNA can be extracted. PMID:27596408

  2. Electrochemical biosensor based on glucose oxidase encapsulated within enzymatically synthesized poly(1,10-phenanthroline-5,6-dione).

    PubMed

    Ciftci, Hakan; Oztekin, Yasemin; Tamer, Ugur; Ramanaviciene, Almira; Ramanavicius, Arunas

    2014-11-01

    This study is focused on the investigation of electrocatalytic effect of glucose oxidase (GOx) immobilized on the graphite rod (GR) electrode. The enzyme modified electrode was prepared by encapsulation of immobilized GOx within enzymatically formed poly(1,10-phenanthroline-5,6-dione) (pPD) film. The electrochemical responses of such enzymatic electrode (pPD/GOx/GR) vs. different glucose concentrations were examined chronoamperometrically in acetate-phosphate buffer solution (A-PBS), pH 6.0, under aerobic or anaerobic conditions. Amperometric signals of the pPD/GOx/GR electrode exhibited well-defined hyperbolic dependence upon glucose concentration. Amperometric signals at 100mM of glucose were 41.17 and 32.27 μA under aerobic and anaerobic conditions, respectively. Amperometric signals of the pPD/GOx/GR electrode decreased by 6% within seven days. The pPD/GOx/GR electrode showed excellent selectivity in the presence of dopamine and uric acid. Furthermore it had a good reproducibility and repeatability with standard deviation of 9.4% and 8.0%, respectively. PMID:25454754

  3. Arabidopsis inositol 1,3,4-trisphosphate 5/6 kinase 2 is required for seed coat development.

    PubMed

    Tang, Yong; Tan, Shutang; Xue, Hongwei

    2013-07-01

    Inositol 1,3,4-trisphosphate 5/6 kinase (ITPK) phosphorylates inositol 1,3,4-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4,6-tetrakisphosphate which can be finally transferred to inositol hexaphosphate (IP₆) and play important roles during plant growth and development. There are 4 putative ITPK members in Arabidopsis. Expression pattern analysis showed that ITPK2 is constitutively expressed in various tissues. A T-DNA knockout mutant of ITPK2 was identified and scanning electron microscopy (SEM) analysis showed that the epidermis structure of seed coat was irregularly formed in seeds of itpk2-1 mutant, resulting in the increased permeability of seed coat to tetrazolium salts. Further analysis by gas chromatography coupled with mass spectrometry of lipid polyester monomers in cell wall confirmed a dramatic decrease in composition of suberin and cutin, which relate to the permeability of seed coat and the formation of which is accompanied with seed coat development. These results indicate that ITPK2 plays an essential role in seed coat development and lipid polyester barrier formation. PMID:23595027

  4. 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. PMID:24953993

  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. Magnetic properties of YMn{sub x}Al{sub 12{minus}x}(x = 4,5,6)

    SciTech Connect

    Coldea, M.; Coldea, R.; Borodi, G.

    1994-03-01

    Magnetic susceptibility of YMn{sub x}Al{sub 12{minus}x} (x=4,5,6) with ThMn{sub 12} structure was measured at temperatures 90K to 900K. These compounds show varied magnetic behaviors depending upon the relative abundance of Mn atoms in the 8f, 8j and 8i crystallographic sites. In the high temperature range, the temperature dependence of the susceptibility is of the Curie-Weiss type. The occurrence of a Mn moment in YMn{sub 4}Al{sub 8} and YMn{sub 8}Al{sub 6} is strongly correlated with the critical value d{approx}2.6{angstrom} of MD-Mn distance below which the Mn moment collapses. In YMn{sub 8}Al{sub 6} both the magnetic and the nonmagnetic Mn atoms were observed to coexist. It has been revealed that the magnetic character of Mn moment in the 8f sites of these two compounds changes from an itinerant electron type to a local moment type with increasing temperature. A transition to a spin glass state at low temperatures for YMn{sub 5}Al{sub 7}, was suggested.

  7. Lipoic acid does not improve renal function markers in 5/6 nephrectomy model: possible role of Nrf2 inactivation.

    PubMed

    Lo, Sze M; Dal Lin, Fernando T; Soares, Maria F; Hauser, Aline B; Pecoits-Filho, Roberto; Nakao, Lia S

    2016-05-01

    Chronic kidney disease (CKD) progression and complications are associated with increased oxidative stress, as well as with Nrf2 inactivation. Lipoic acid (LA) has been considered an inducer of Nrf2 antioxidant response. We tested whether oral administration of LA provides beneficial effects in experimental CKD in rats. Wistar rats underwent 5/6 nephrectomy (CKD group) or sham laparotomy. Seven days later, CKD group was divided into three subgroups that received: (i) LA continuously in the drinking water (100 mg/kg/day), (ii) LA by gavage every other day (100 mg/kg), or (iii) no LA treatment. LA treatment lasted until day 60. Plasma urea and creatinine, 24 h-proteinuria, glomerulosclerosis, interstitial fibrosis/tubular atrophy, and Nrf2 activation were analyzed. All parameters measured were significantly altered in the untreated CKD group, compared with the sham group, as expected. Oral LA administration, either in the drinking water or by gavage, did not improve significantly any parameter, comparing the treated-groups with the untreated CKD group. These results indicate that oral LA administration for 53 days was ineffective to reactivate Nrf2 in the remnant kidney of uremic rats, likely preventing improvements in biochemical and histopathological markers of renal function. PMID:26904958

  8. Improved propionic acid and 5,6-dimethylbenzimidazole control strategy for vitamin B12 fermentation by Propionibacterium freudenreichii.

    PubMed

    Wang, Peng; Zhang, Zhiwei; Jiao, Youjing; Liu, Shouxin; Wang, Yunshan

    2015-01-10

    An efficient fermentation-strengthening approach was developed to improve the anaerobic production of vitamin B12 by cultivation process optimization with Propionibacterium freudenreichii. The effects of the byproduct propionic acid and the precursor 5,6-dimethylbenzimidazole (DMB) on vitamin B12 biosynthesis were investigated. Byproduct inhibition experiments showed that maintaining propionic acid concentration in broth below 10-20 g/L in the early stage and 20-30 g/L in the late stage can efficiently improve vitamin B12 biosynthesis. Batch fermentation indicated the occurrence of feed-back inhibition in intracellular intermediate biosynthesis. In addition, the incorporation of the precursor DMB depended on the fermentation level of the vitamin B12 intermediate. High vitamin B12 concentration (58.8 mg/L) and production (0.37 mg/g) were obtained with an expanded bed adsorption bioreactor by using the propionic acid and DMB control method. The optimum concentration and production of 59.5 and 0.59 mg/L h for vitamin B12 production were respectively achieved after five continuous batches. PMID:25455014

  9. 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.

  10. Synthesis and anticancer activities of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline derivatives.

    PubMed

    Zhang, Ying; Jin, Linhong; Xiang, Hongmei; Wu, Jian; Wang, Peiyi; Hu, Deyu; Xue, Wei; Yang, Song

    2013-08-01

    A series of 5,6,7-trimethoxy-N-phenyl(ethyl)-4-aminoquinazoline compounds was prepared by microwave irradiation and conventional heating methods. Compounds 6p, 6q, and 6x strongly inhibited extracellular regulated kinase1/2 (ERK1/2) phosphorylation induced by epidermal growth factor (EGF) at 1.28 μM in PC3 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all compounds had certain anticancer activities, and the IC₅₀ values of 6x were 6.2 ± 0.9, 3.2 ± 0.1, and 3.1 ± 0.1 μM against PC3, BGC823, and Bcap37 cells, respectively. Acridine orange/ethidium bromide staining, Hoechst 33258 staining, DNA ladder, and flow cytometry analyses revealed that 6x induced cell apoptosis in PC3 cells, with apoptosis ratios of 11.6% at 1 μM and 31.8% at 10 μM after 72 h. PMID:23811258

  11. Electron density determinations of stellar coronae using Fe XXI ndarrow2p (n=3,4,5,6) transitions

    NASA Astrophysics Data System (ADS)

    Chen, H.; Beiersdorfer, P.; Liedahl, D. A.; Bitter, M.; Brown, G. V.; Kahn, S. M.

    2002-04-01

    The idea of using L-shell iron spectroscopic information to infer the electron density has become very attractive following the availability of high-resolution data measured by current x-ray observatories. Following suggestions in [1], we developed the n darrow2p line (n=3,4,5,6) intensities in Fe XXI as a diagnostic that is sensitive to densities near 10^13 cm-3 and applied it to Chandra observations of HR1099. HULLAC code predictions of the density sensitivity were checked with the Livermore EBIT-II ion trap for low densities. Checks at high density are in progress at the Princeton NSTX tokamak. For HR1099 we find a density of about 2 to 8 x 10^13 cm-3. This is in the range of 10^12 - 10^13 cm-3 that was determined using the Fe XXI EUV line ratios (102/128 ÅÅobserved with EUVE [2]. This work was performed under the auspice of DOE by UC-LLNL under contract W-7405-Eng-48 and supported by DOE OFES and by NASA SARA grants to LLNL, GSFC, PPPL and Columbia University.\\$[1]. Wargelin, et al, APJ 496 (1998). [2]. Ayres,et al, APJ, 549, (2001) 554)

  12. Higher Education in Arkansas.

    ERIC Educational Resources Information Center

    Arkansas State Dept. of Higher Education, Little Rock.

    This report presents information about higher education in Arkansas. Arkansas is 49th in the United States in the number of citizens over the age of 25 with a baccalaureate or higher degree. Arkansas faces shortages of qualified teachers and nurses in regions of the state at a time when the number of graduates in these professions is declining…

  13. 5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

    PubMed Central

    van Koppen, Arianne; Verhaar, Marianne C.; Bongartz, Lennart G.; Joles, Jaap A.

    2013-01-01

    Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological

  14. 5/6th nephrectomy in combination with high salt diet and nitric oxide synthase inhibition to induce chronic kidney disease in the Lewis rat.

    PubMed

    van Koppen, Arianne; Verhaar, Marianne C; Bongartz, Lennart G; Joles, Jaap A

    2013-01-01

    Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological

  15. 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

    2008-09-01

    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. PMID:18698710

  16. 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

  17. 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. PMID:24147122

  18. Determinants of the abilities to jump higher and shorten the contact time in a running 1-legged vertical jump in basketball.

    PubMed

    Miura, Ken; Yamamoto, Masayoshi; Tamaki, Hiroyuki; Zushi, Koji

    2010-01-01

    This study was conducted to obtain useful information for developing training techniques for the running 1-legged vertical jump in basketball (lay-up shot jump). The ability to perform the lay-up shot jump and various basic jumps was measured by testing 19 male basketball players. The basic jumps consisted of the 1-legged repeated rebound jump, the 2-legged repeated rebound jump, and the countermovement jump. Jumping height, contact time, and jumping index (jumping height/contact time) were measured and calculated using a contact mat/computer system that recorded the contact and air times. The jumping index indicates power. No significant correlation existed between the jumping height and contact time of the lay-up shot jump, the 2 components of the lay-up shot jump index. As a result, jumping height and contact time were found to be mutually independent abilities. The relationships in contact time between the lay-up shot jump to the 1-legged repeated rebound jump and the 2-legged repeated rebound jump were correlated on the same significance levels (p < 0.05). A significant correlation for jumping height existed between the 1-legged repeated rebound jump and the lay-up shot jump (p < 0.05), although none existed for jumping height between the lay-up shot jump and both the 2-legged repeated rebound jump and countermovement jump. The lay-up shot index correlated more strongly to the 1-legged repeated rebound jump index (p < 0.01) when compared to the 2-legged repeated rebound jump index (p < 0.05). These results suggest that the 1-legged repeated rebound jump is effective in improving both contact time and jumping height in the lay-up shot jump. PMID:19996782

  19. 40 CFR 721.9503 - Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxy-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9503 Silane, (3,3,4,4,5,5,6,6,7,7,8,8... subject to reporting. (1) The chemical substance identified as silane,...

  20. 40 CFR 721.9503 - Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxy-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9503 Silane, (3,3,4,4,5,5,6,6,7,7,8,8... subject to reporting. (1) The chemical substance identified as silane,...

  1. 40 CFR 721.9503 - Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxy-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9503 Silane, (3,3,4,4,5,5,6,6,7,7,8,8... subject to reporting. (1) The chemical substance identified as silane,...

  2. 40 CFR 721.9503 - Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxy-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9503 Silane, (3,3,4,4,5,5,6,6,7,7,8,8... subject to reporting. (1) The chemical substance identified as silane,...

  3. 40 CFR 721.9503 - Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)trimethoxy-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Silane, (3,3,4,4,5,5,6,6,7,7,8,8,9,9... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9503 Silane, (3,3,4,4,5,5,6,6,7,7,8,8... subject to reporting. (1) The chemical substance identified as silane,...

  4. In Vitro Reconstitution of the Toll/Interleukin-1 Receptor (TIR) Domain Complex Between TLR5/6 and Myd88.

    PubMed

    Jang, Tae-Ho; Narayanan, Kannan Badri; Park, Hyun Ho

    2016-01-01

    Toll-like receptors (TLRs) are evolutionarily conserved receptors with trimodular structure to respond to endogenous ligands and exogenous ligands from microbial pathogens. The highly conserved cytoplasmic C-terminal Toll/interleukin-1 receptor (TIR) domain of TLRs plays a crucial role in inflammatory reactions. In myeloid differentiation primary-response protein 88 (MyD88)- dependent signaling pathway, the interaction of TLRsTIR with cytosolic adaptor protein, MyD88TIR recruits IL-1R-associated kinases (IRAK) for subsequent activation of transcription factors nuclear factor kB (NF-kB) and activation protein 1 (AP-1) and other effector molecules. In the present investigation, TLR5TIR, TLR6TIR and MyD88TIR genes were subcloned and overexpressed in bacterium Escherichia coli strain BL- 21 (DE3). The purification and biochemical characterization of TLR5TIR and TLR6TIR&, and MyD88TIR proteins were also performed. The protein-protein interactions between TIR domains of TLR5 and TLR6 with MyD88, respectively, were evaluated in vitro at physiological pH and salt concentration. The in vitro reconstitution results showed that under physiological pH and salt concentration, MyD88TIR interacted with TLR5TIR, and did not interact with TLR6TIR protein. Both TIR domain-containing TLR5 and TLR6 proteins were prone to aggregation in a temperature-dependent manner at room temperature. At normal physiological pH and salt concentration, with the addition of binding partner MyD88TIR to TLR5/6TIR, time-dependent aggregation was not observed in both TLRsTIR at both room temperature and 4 ºC for 2 d, influencing the solubility of TLR5/6TIR. Moreover, TLR5TIR alone exhibited increase in solubility of the protein with increase in the salt concentration of the buffered solution from 0.025 M to 1.25 M at room temperature. PMID:26548862

  5. Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

    PubMed Central

    Bermúdez-López, Marcelino; Villoria, María Teresa; Esteras, Miguel; Jarmuz, Adam; Torres-Rosell, Jordi; Clemente-Blanco, Andres; Aragon, Luis

    2016-01-01

    The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, from end resection to Holliday junction (HJ) dissolution. Sgs1 has both pro- and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1–Top3–Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1's recombination functions. PMID:27298337

  6. 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. PMID:27455833

  7. 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. PMID:26421921

  8. 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.

  9. 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.

  10. Molecular and crystal structures of some novel derivatives of 3-aryl-7-arylidene-3,3a,4,5,6,7-hexahydroindazoles

    SciTech Connect

    Abakumov, V. V.; Shishkina, S. V.; Zubatyuk, R. I.; Gella, I. M.; Pivnenko, N. S.; Kutulya, L. A. Shishkin, O. V.

    2007-03-15

    The stereochemical aspects of the interaction of 2,6-bis(arylidene)-cyclohexanone and 2,6-bis(arylidene)-3-methylcyclohexanone with arylhydrazine (aryl is phenyl or 4-nitrophenyl) and methylhydrazine are investigated using X-ray diffraction analysis. The molecular structure of the 3-aryl-7-arylidene-3,3a,4,5,6,7-hexahydroindazoles synthesized is determined by X-ray diffraction analysis for the first time. It is established that the stereochemistry of the products of the interaction between the cyclohexanone derivatives and arylhydrazines depends on the electronic nature of the substituent in the aryl group. Two regioisomeric products with different positions of the methyl group in the cyclohexane ring with respect to the arylidene fragment are synthesized by the reaction of 2,6-bis(4-methoxybenzylidene)-3-methylcyclohexanone with methylhydrazine. The influence of the substituents at the nitrogen atom of the pyrazoline ring on the intramolecular electronic interactions and the geometry of the heterocycle in the compounds under investigation is discussed.

  11. 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) . PMID:27061761

  12. 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. PMID:24662760

  13. 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.

  14. [Longer waiting time and higher mortality in older people with traumatic brain injuries. Mapping of emergency prehospital management and hospital management in Västerbotten].

    PubMed

    Holzmann, Martin; Bylund, Per O; Degerfält, Lisa; Carlsson, Axel C; Wändell, Per; Ruge, Toralph

    2015-01-01

    The main purpose was to study the prehospital and early intrahospital treatment of patients with traumatic brain injury (TBI) in the county of Västerbotten 2011-2012. In total, 162 patients were included. The main finding was that a large proportion of TBI patients were older men who fell in the same or from a different level. Older patients had higher mortality and had to wait longer for diagnostic imaging compared to younger patients. Furthermore, most patients were initially relatively unaffected by the injury and around 1/5 of the patients were transported to hospital by private transport. Finally, we observed that most patients were admitted to hospital and computer tomography scan of the head was performed within 4 hours. PMID:26440946

  15. Focusing Cosmic Telescopes: Exploring Redshift z ~ 5-6 Galaxies with the Bullet Cluster 1E0657 - 56

    NASA Astrophysics Data System (ADS)

    Bradač, Maruša; Treu, Tommaso; Applegate, Douglas; Gonzalez, Anthony H.; Clowe, Douglas; Forman, William; Jones, Christine; Marshall, Phil; 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 ~ 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. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5

  16. 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

  17. 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. PMID:25913075

  18. Assessment of the Early Effects of 5,6-Dimethylxanthenone-4-Acetic Acid Using Macromolecular Contrast Media-Enhanced Magnetic Resonance Imaging: Ectopic Versus Orthotopic Tumors

    SciTech Connect

    Seshadri, Mukund Bellnier, David A.; Cheney, Richard T.

    2008-11-15

    Purpose: To investigate the early effects of a vascular disrupting agent (VDA) in ectopic and orthotopic tumors by using macromolecular contrast media (MMCM)-enhanced magnetic resonance imaging (MMCM-MRI). Methods and Materials: The MMCM-MRI of ectopic and orthotopic MCA205 murine fibrosarcomas was performed using the intravascular contrast agent albumin-(gadopentetate dimeglumine){sub 35}. Change in longitudinal relaxation rate ({delta}R1) was measured 24 hours after treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA; 30 mg/kg) and used to compute tumor vascular volume and permeability. Correlative histologic and immunohistochemical evaluation was carried out, along with measurement of tumor necrosis factor {alpha} and vascular endothelial growth factor levels in whole tumor extracts using the enzyme-linked immunosorbent assay. Results: Orthotopic tumors showed higher vascular volume (p < 0.05) than ectopic tumors before treatment. Twenty-four hours after DMXAA treatment, a significant (p < 0.0001), but differential, decrease in {delta}R1 (70% in ectopic and 50% in orthotopic tumors) was observed compared with baseline estimates. Consistent with this observation, greater levels of tumor necrosis factor {alpha}, an important mediator of the antivascular activity of DMXAA, were measured in ectopic tumors 3 hours posttreatment compared with orthotopic tumors (p < 0.05). Immunohistochemical (CD31) and histologic (hematoxylin and eosin) sections of ectopic and orthotopic tumors showed highly tumor-selective vascular damage after treatment with the presence of viable surrounding normal tissue. Conclusions: The MMCM-MRI provided early quantitative estimates of change in tumor perfusion after VDA treatment that showed good correlation with cytokine induction. Differences in the response of ectopic and orthotopic tumors highlight the influence of the host microenvironment in modulating the activity of VDAs.

  19. In vitro activities of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone against non-small cell lung carcinoma.

    PubMed

    Feng, Shi-Xiu; Guan, Qiunong; Chen, Tao; Du, Caigan

    2012-07-01

    Medicinal herbs are the preferred candidates for drug discovery against human diseases including cancer. The roots of Prismatomeris connata have been used in traditional herbal medicine to treat many health problems, particularly pneumoconiosis. This study was to test the anti-tumor activity of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone (PCON6), a major anthraquinone derivative from C. connata, against lung cancer. Cell viability in cultures was assessed by MTT assay. Cell death or apoptosis was determined with annexin-V and 7-aminoactinomycin D staining. Cell cycle was analyzed by both propidium iodide DNA staining and BrdU incorporation assay. Here we showed that in a panel of fifteen different tumor cells lines, a group of four non-small cell lung carcinoma (NSCLC) cell lines exhibited a relatively higher sensitivity to PCON6 growth inhibition than the rest of most non-lung cancer cell lines (p = 0.0461). Further studies demonstrated that the suppression of NSCLC H520 cell growth by PCON6 was associated with its induction of apoptosis at 20 μM (p = 0.0008), and of cell accumulation at S phase cell cycle (p < 0.05) that was further supported by a decrease in cdc2 protein expression. This preliminary study suggests that natural compound PCON6 has relatively selective cytotoxicity against NSCLC growth and represent a concept of developing a novel drug therapy specific for NSCLC based on the roots of C. connata or PCON6. PMID:22864748

  20. Prevalence of Bloodstream Pathogens Is Higher in Neonatal Encephalopathy Cases vs. Controls Using a Novel Panel of Real-Time PCR Assays

    PubMed Central

    Tann, Cally J.; Nkurunziza, Peter; Nakakeeto, Margaret; Oweka, James; Kurinczuk, Jennifer J.; Were, Jackson; Nyombi, Natasha; Hughes, Peter; Willey, Barbara A.; Elliott, Alison M.; Robertson, Nicola J.; Klein, Nigel; Harris, Kathryn A.

    2014-01-01

    Background In neonatal encephalopathy (NE), infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda. Methodology Multiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV), herpes simplex virus(HSV) and P. falciparum) were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC) was performed for all cases and unwell controls. Principal Findings Prevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028) using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae). Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively). Conclusion/Significance This real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting. PMID:24836781

  1. 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.

  2. 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…

  3. 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

  4. 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.

  5. 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. PMID:27450807

  6. Modulation of activity and substrate binding modes by mutation of single and double subsites +1/+2 and -5/-6 of barley alpha-amylase 1.

    PubMed

    Mori, H; Bak-Jensen, K S; Gottschalk, T E; Motawia, M S; Damager, I; Møller, B L; Svensson, B

    2001-12-01

    Enzymatic properties of barley alpha-amylase 1 (AMY1) are altered as a result of amino acid substitutions at subsites -5/-6 (Cys95-->Ala/Thr) and +1/+2 (Met298-->Ala/Asn/Ser) as well as in the double mutants, Cys95-->Ala/Met298-->Ala/Asn/Ser. Cys95-->Ala shows 176% activity towards insoluble Blue Starch compared to wild-type AMY1, kcat of 142 and 211% towards amylose DP17 and 2-chloro-4-nitrophenyl beta-d-maltoheptaoside (Cl-PNPG7), respectively, but fivefold to 20-fold higher Km. The Cys95-->Thr-AMY1 AMY2 isozyme mimic exhibits the intermediary behaviour of Cys95-->Ala and wild-type. Met298-->Ala/Asn/Ser have slightly higher to slightly lower activity for starch and amylose, whereas kcat and kcat/Km for Cl-PNPG7 are < or = 30% and < or = 10% of wild-type, respectively. The activity of Cys95-->Ala/Met298-->Ala/Asn/Ser is 100-180% towards starch, and the kcat/Km is 15-30%, and 0.4-1.1% towards amylose and Cl-PNPG7, respectively, emphasizing the strong impact of the Cys95-->Ala mutation on activity. The mutants therefore prefer the longer substrates and the specificity ratios of starch/Cl-PNPG7 and amylose/Cl-PNPG7 are 2.8- to 270-fold and 1.2- to 60-fold larger, respectively, than of wild-type. Bond cleavage analyses show that Cys95 and Met298 mutations weaken malto-oligosaccharide binding near subsites -5 and +2, respectively. In the crystal structure Met298 CE and SD (i.e., the side chain methyl group and sulfur atom) are near C(6) and O(6) of the rings of the inhibitor acarbose at subsites +1 and +2, respectively, and Met298 mutants prefer amylose for glycogen, which is hydrolysed with a slightly lower activity than by wild-type. Met298 AMY1 mutants and wild-type release glucose from the nonreducing end of the main-chain of 6"'-maltotriosyl-maltohexaose thus covering subsites -1 to +5, while productive binding of unbranched substrate involves subsites -3 to +3. PMID:11737209

  7. Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats.

    PubMed

    Zhang, Yue-Yue; Huang, Juan; Yang, Man; Gu, Li-Jie; Ji, Jia-Yao; Wang, Li-Jun; Yuan, Wei-Jie

    2015-01-01

    Ketoacids (KA) are known to preserve muscle mass among patients with chronic kidney disease (CKD) on a low-protein diet (LPD). The present study was to compare the effects of KA supplemented diet therapy in autophagy and inflammation in CKD rats' skeletal muscle. Rats with 5/6 nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day protein [normal-protein diet (NPD)], 3 g/kg/day protein (LPD) or 3 g/kg/day protein which including 5% protein plus 1% KA (LPD + KA) for 24 weeks. Sham-operated rats with NPD intake were used as control. LPD could improve body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (microtubule-associated protein 1 light chain 3), p62, Parkin and PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total mtDNA (mitochondiral DNA) and cytosol mtDNA, NACHT-PYD-containing protein 3 (NALP3) inflammasome than LPD group, but its reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1β (interleukin-1-beta) was lower in LPD and LPD + KA group than the NPD group, but IL-18 showed no significant difference among control and CKD group; toll-like receptor signalling-dependent IL-6 was higher in LPD + KA group than LPD group, but tumor necrosis factor-α (TNF-α) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating inflammation to provide new therapeutic approaches for CKD protein energy wasting (PEW). PMID:26371333

  8. Selection and Validation of Reference Genes for Quantitative Real-Time Polymerase Chain Reaction Studies in Mossy Maze Polypore, Cerrena unicolor (Higher Basidiomycetes).

    PubMed

    Yang, Jie; Lin, Qi; Lin, Juan; Ye, Xiuyun

    2016-01-01

    With its ability to produce ligninolytic enzymes such as laccases, white-rot basidiomycete Cerrena unicolor, a medicinal mushroom, has great potential in biotechnology. Elucidation of the expression profiles of genes encoding ligninolytic enzymes are important for increasing their production. Quantitative real-time polymerase chain reaction (qPCR) is a powerful tool to study transcriptional regulation of genes of interest. To ensure accuracy and reliability of qPCR analysis of C. unicolor, expression levels of seven candidate reference genes were studied at different growth phases, under various induction conditions, and with a range of carbon/nitrogen ratios and carbon and nitrogen sources. The stability of the genes were analyzed with five statistical approaches, namely geNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder. Our results indicated that the selection of reference genes varied with sample sets. A combination of four reference genes (Cyt-c, ATP6, TEF1, and β-tubulin) were recommended for normalizing gene expression at different growth phases. GAPDH and Cyt-c were the appropriate reference genes under different induction conditions. ATP6 and TEF1 were most stable in fermentation media with various carbon/nitrogen ratios. In the fermentation media with various carbon or nitrogen sources, 18S rRNA and GAPDH were the references of choice. The present study represents the first validation analysis of reference genes in C. unicolor and serves as a foundation for its qPCR analysis. PMID:27279538

  9. 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…

  10. 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. PMID:27083282

  11. 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. PMID:27010650

  12. 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 Central

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

    2016-01-01

    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. PMID:27010650

  13. 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.

  14. 5,6-Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent.

    PubMed

    McKeage, Mark J; Fong, Peter; Jeffery, Mark; Baguley, Bruce C; Kestell, Phil; Ravic, Miroslav; Jameson, Michael B

    2006-03-15

    This phase I safety study aimed to identify the optimal dose of the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) for combination studies. Using a crossover design, 15 patients with refractory tumors were allocated randomly to receive six sequential doses of DMXAA (300, 600, 1,200, 1,800, 2,400, and 3,000 mg m(-2)), each given once-weekly as a 20-minute i.v. infusion. The drug was generally well tolerated. Transient, moderate increases in the heart rate-corrected cardiac QT interval occurred at the two highest doses. DMXAA produced transient dose-dependent increases in blood pressure. Transient, dose-related visual disturbances occurred at the two highest doses. No significant changes in K(trans) and k(ep) were observed but V(e), a secondary dynamic contrast-enhanced magnetic resonance imaging variable, increased significantly after giving DMXAA. At 1,200 mg m(-2), the Cmax and the area under the concentration-time curve over 24 hours for total and free DMXAA plasma concentrations were 315 +/- 25.8 microg/mL, 29 +/- 6.4 microg/mL x d, 8.0 +/- 1.77 microg/mL, and 0.43 +/- 0.07 microg/mL x d, respectively. Plasma levels of the vascular damage biomarker 5-hydroxyindoleacetic acid increased in the 4 hours after treatment in a dose-dependent fashion up to 1,200 mg m(-2), with a plateau thereafter. Doses in the range of 1,200 mg m(-2) have been selected for further studies (phase II combination studies with taxanes and platins are under way) because this dose produced no significant effect on heart rate-corrected cardiac QT interval, produced near maximum levels of 5-hydroxyindoleacetic acid, achieved DMXAA plasma concentrations within the preclinical therapeutic range, and was well tolerated. PMID:16551862

  15. 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

  16. 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).

  17. 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…

  18. PHOTOLYSIS RATES OF (2,4,5-TRICHLOROPHENOXY)ACETIC ACID AND 4-AMINO-3,5,6-TRICHLOROPICOLINIC ACID IN NATURAL WATERS

    EPA Science Inventory

    Photoreactions of (2,45-trichlorophenoxy) acetic acid (2,4,5-T) and 4-amino-3,5,6-trichloropicolinic acid (picloram) were studied in distilled water, natural water samples, fulvic acid solutions, and solutions containing iron (III) and/or hydrogen peroxide to determine the effect...

  19. 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...

  20. A ONE STEP METHOD FOR THE DETERMINATION OF CARBAMATE PESTICIDES BY DERIVATIZATION WITH ALPHA-BROMO-2,3,4,5,6-PENTAFLUOROTOLUENE

    EPA Science Inventory

    A procedure was developed for the determination of trace quantities of a broad range of carbamate pesticides. The carbamates were hydrolyzed and derivatized in a single step, using alkali and alpha-bromo-2,3,4,5,6-pentafluorotoluene (PFBB), and were subsequently analyzed using el...

  1. The Effect Inclusive Education Practice during Preschool Has on the Peer Relations and Social Skills of 5-6-Year Olds with Typical Development

    ERIC Educational Resources Information Center

    Ogelman, Hulya Gulay; Secer, Zarife

    2012-01-01

    The purpose of this study is to set forth the effect preschool inclusive education practices have on the peer relations of 5-6 year olds with typical development. The study comprised of two sample groups. The children in both groups were attendees of kindergartens at primary schools governed by the Ministry of National Education located in the…

  2. 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…

  3. Synthesis and anti-inflammatory activity of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives.

    PubMed

    Jakubkiene, Virginija; Burbuliene, Milda Malvina; Mekuskiene, Giedrute; Udrenaite, Emilija; Gaidelis, Povilas; Vainilavicius, Povilas

    2003-04-01

    The synthesis of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-2,3-dihydro-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives and the results of anti-inflammatory activity in vivo are described. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than acetylsalicylic acid. PMID:12727542

  4. 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 ...

  5. 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...

  6. Relaxation of the V = 4,5,6,7, Sigma g/+/ vibrational levels of carbon monoxide studied by laser absorption.

    NASA Technical Reports Server (NTRS)

    Chackerian, C., Jr.; Weisbach, M. F.

    1973-01-01

    The vibrational relaxation of individual vibration rotation levels of carbon monoxide behind incident shock waves of carbon monoxide has been studied by the method of laser absorption. For the particular vibrational states (V = 4 to 7) and temperature range (2500 to 5500 K) studied, it is concluded that the characteristic relaxation times are in excellent agreement with those obtained via previous measurements of 'bulk' gas properties. Further, the data furnish strong corroboration of the idea that the individual levels are in Boltzmann vibrational equilibrium during the relaxation process.

  7. 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

  8. 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

  9. 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…

  10. Density functional theory and Raman spectroscopy applied to structure and vibrational mode analysis of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro- benzimidazolocarbocyanine iodide and its aggregate.

    PubMed

    Aydin, Metin; Dede, Özge; Akins, Daniel L

    2011-02-14

    We have measured electronic and Raman scattering spectra of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro-benzimidazolocarbocyanine iodide (TTBC) in various environments, and we have calculated the ground state geometric and spectroscopic properties of the TTBC cation in the gas and solution phases (e.g., bond distances, bond angles, charge distributions, and Raman vibrational frequencies) using density functional theory. Our structure calculations have shown that the ground state equilibrium structure of a cis-conformer lies ∼200 cm(-1) above that of a trans-conformer and both conformers have C(2) symmetry. Calculated electronic transitions indicate that the difference between the first transitions of the two conformers is about 130 cm(-1). Raman spectral assignments of monomeric- and aggregated-TTBC cations have been aided by density functional calculations at the same level of the theory. Vibrational mode analyses of the calculated Raman spectra reveal that the observed Raman bands above 700 cm(-1) are mainly associated with the in-plane deformation of the benzimidazolo moieties, while bands below 700 cm(-1) are associated with out-of-plane deformations of the benzimidazolo moieties. We have also found that for the nonresonance excited experimental Raman spectrum of aggregated-TTBC cation, the Raman bands in the higher-frequency region are enhanced compared with those in the nonresonance spectrum of the monomeric cation. For the experimental Raman spectrum of the aggregate under resonance excitation, however, we find new Raman features below 600 cm(-1), in addition to a significantly enhanced Raman peak at 671 cm(-1) that are associated with out-of-plane distortions. Also, time-dependent density functional theory calculations suggest that the experimentally observed electronic transition at ∼515 nm (i.e., 2.41 eV) in the absorption spectrum of the monomeric-TTBC cation predominantly results from the π → π∗ transition. Calculations are further interpreted

  11. 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.

  12. 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

    2010-06-01

    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 (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. PMID:20463374

  13. Higher Education in the Eighties.

    ERIC Educational Resources Information Center

    McComas, James D.

    Events and conditions over the last 20 years that have altered the course of higher education are briefly noted, and trends in higher education for the early eighties are examined. Among the past influences on higher education that illustrate the wisdom of planning for a realistic period of time, such as five years, are the following: the massive…

  14. 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…

  15. 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.

    PubMed

    Morgan, Marsha K

    2015-07-01

    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 (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20-49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4-6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥ 89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults' ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults' ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults' ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0

  16. Simultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran from Sophora tonkinensis in rat plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

    PubMed

    Yoo, Hunseung; Ryu, Keun Ho; Bae, Soo Kyung; Kim, Jinwoong

    2014-11-01

    A new liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran from Sophora tonkinensis in rat plasma using chlorpropamide as an internal standard. Plasma samples (50 μL) were prepared using a simple deproteinization procedure with 150 μL of acetonitrile containing 100 ng/mL of chlorpropamide. Chromatographic separation was carried out on an Acclaim RSLC120 C18 column (2.1 × 100 mm, 2.2 μm) using a gradient elution consisting of 7.5 mM ammonium acetate and acetonitrile containing 0.1% formic acid (0.4 mL/min flow rate, 7.0 min total run time). The detection and quantitation of all analytes were performed in selected reaction monitoring mode under both positive and negative electrospray ionization. This assay was linear over concentration ranges of 50-5000 ng/mL (trifolirhizin), 25-2500 ng/mL ((-)-maackiain), 5-250 ng/mL ((-)-sophoranone), and 1-250 ng/mL 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran) with a lower limit of quantification of 50, 25, 5, and 1 ng/mL for trifolirhizin, (-)-maackiain, (-)-sophoranone, and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, respectively. All the validation data, including the specificity, precision, accuracy, recovery, and stability conformed to the acceptance requirements. The results indicated that the developed method is sufficiently reliable for the pharmacokinetic study of the analytes following oral administration of Sophora tonkinensis extract in rats. PMID:25156071

  17. 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.

  18. The Reactivity of Thymine and Thymidine 5,6-Epoxides with Organometallic Reagents - A Route to Thymidine (6-4) Photoproduct Analogues.

    PubMed

    Wrigstedt, Pauli; Kavakka, Jari; Heikkinen, Sami; Nieger, Martin; Räisänen, Minna; Repo, Timo

    2016-05-01

    This report describes an efficient procedure for the generation and isolation of various thymine and thymidine 5,6-epoxides from the corresponding trans-5,6-bromohydrins by reaction with triethylamine. The quantitative isolation of the epoxides, accomplished by solvent precipitation of triethylamine hydrobromide, enabled their regiospecific ring-opening at C6 position by organometallic nucleophiles. The reaction was amenable to a broad range of alkyl, aryl, alkenyl, and alkynyl organomagnesium, -zinc, -aluminum, or -boron reagents, although the reactivity was strongly affected by the electronic effects of N3 protecting group. Additionally, the reaction featured excellent cis-diastereoselectivity providing access to C6-carbon-functionalized dihydrothymidine cis-alcohols, which are synthetic derivatives of UV-induced DNA lesions, namely, thymidine (6-4) photoproducts. PMID:27080560

  19. Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.

    PubMed

    Xie, Wenlin; Xie, Shimin; Zhou, Ying; Tang, Xufu; Liu, Jian; Yang, Wenqian; Qiu, Minghua

    2014-06-23

    A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed. PMID:24819956

  20. 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. PMID:26224602

  1. 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

  2. The unique luminal staining pattern of cytokeratin 5/6 in adenoid cystic carcinoma of the breast may aid in differentiating it from its mimickers.

    PubMed

    Nakai, Tokiko; Ichihara, Shu; Kada, Akiko; Ito, Noriko; Moritani, Suzuko; Kawasaki, Tomonori; Uchiyama, Tomoko; Itami, Hiroe; Morita, Kouhei; Takano, Masato; Takeda, Maiko; Hatakeyama, Kinta; Ohbayashi, Chiho

    2016-08-01

    Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis. PMID:27240462

  3. Structural studies on Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene. An UV, IR, NMR and DFT study. A mini-review

    NASA Astrophysics Data System (ADS)

    Hansen, Poul Erik; Spanget-Larsen, Jens

    2016-09-01

    Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene are chosen as an exemplary case for tautomeric Mannich bases. Molecular structures are calculated. OH stretching frequencies are rationalized based on DFT calculations. Intrinsic deuterium isotope effects on 13C chemical shifts in the M-form are estimated based on OH bond lengths. The observed deuterium isotope effects on 13C chemical shifts are demonstrated to be largely of equilibrium type except at ambient temperatures.

  4. Mesd Is a Universal Inhibitor of Wnt Co-receptor LRP5/6 and Blocks Wnt/β-catenin Signaling in Cancer Cells†

    PubMed Central

    Lu, Wenyan; Liu, Chia-Chen; Thottassery, Jaideep V.; Bu, Guojun; Li, Yonghe

    2010-01-01

    Mesd is a specialized chaperone for the low-density lipoprotein receptor-related protein-5 (LRP5) and LRP6. In our previous studies, we found that Mesd binds to mature LRP6 on the cell surface and blocks the binding of Wnt antagonist Dickkopf-1(Dkk1) to LRP6. Herein, we demonstrated that Mesd also binds to LRP5 with a high affinity, and is a universal inhibitor of LRP5/6 ligands. Mesd not only blocks Wnt antagonists Dkk1 and Sclerostin binding to LRP5/6, but also inhibits Wnt3A and Rspondin1-induced Wnt/β-catenin signaling in LRP5/6 expressing cells. We also found that Mesd, Dkk1 and Sclerostin compete with one another for binding to LRP5 and LRP6 at the cell surface. More importantly, we demonstrated that Mesd is able to suppress LRP6 phosphorylation and Wnt/β-catenin signaling in prostate cancer PC-3 cells, and inhibits PC-3 cell proliferation. Our results indicate that recombinant Mesd protein is a useful tool for studying Wnt/β-catenin signaling on the cell surface, and has a potential therapeutic role in Wnt-dependent cancers. PMID:20446724

  5. [(Pb6I8){Mn(CO)5}6](2-): an octahedral (M6X8)-like cluster with inverted bonding.

    PubMed

    Wolf, Silke; Reiter, Kevin; Weigend, Florian; Klopper, Wim; Feldmann, Claus

    2015-04-20

    [BMIm]2[{PbMn(CO)5)}6I8] (BMIm: 1-butyl-3-methylimidazolium) is obtained by ionic liquid mediated reaction of PbI2 and Mn2(CO)10. Central is a cubelike (Pb6I8) unit containing a nonfilled Pb6 octahedron. Each Pb of this (Pb6I8) unit is terminated on its outside by Mn(CO)5, exhibiting Pb-Mn metal-to-metal bonding (280 pm). Structurally, the (Pb6I8) unit is similar to the well-known octahedral (M6Xn) cluster-type family (M = Zr, Nb, Ta, Mo, W; X = Cl, Br, I). In contrast to most similar cluster compounds, such as W6Br12 ([W6Br8]Br2/1Br4/2, according to Niggli notation) or the carbonyl cluster [Sn6{Cr(CO5)6}](2-), however, the nonfilled central Pb6 octahedron in [{PbMn(CO)5)}6I8](2-) does not exhibit any metal-to-metal bonding. Structure and bonding of the title compound are validated by single-crystal structure analysis, energy-dispersive X-ray analysis (EDX), infrared spectroscopy (FT-IR), and density functional theory (DFT) calculations. Based on the isolobal principle, electronegativity considerations, bond lengths, and DFT calculations including Mulliken population analysis and natural population analysis (NPA), in sum, the charge distribution of Pb is best reflected by an oxidation state of +1. PMID:25830920

  6. 4′-CyanoPLP presents better prospect for the experimental detection of elusive cyclic intermediate radical in the reaction of lysine 5,6-aminomutase

    SciTech Connect

    Maity, Amarendra Nath; Ke, Shyue-Chu

    2015-02-06

    Graphical abstract: The results of our calculations suggest that the reaction of 4′-cyanoPLP with lysine 5,6-aminomutase offers better prospect for the experimental detection of elusive cyclic azacyclopropylcarbinyl radical, which is proposed to be a key intermediate in the reaction of pyridoxal-5′-phosphate dependent radical aminomutases. - Highlights: • 4′-CyanoI{sup ·} is the lowest energy radical intermediate in the reaction of 5,6-LAM. • 4′-CyanoPLP offers good prospect for the experimental observation of elusive I{sup ·}. • The calculated HFCCs would help to characterize 4′-cyanoI{sup ·} by EPR. - Abstract: The results of our calculations suggest that the reaction of 4′-cyanoPLP with lysine 5,6-aminomutase offers better prospect for the experimental detection of elusive cyclic azacyclopropylcarbinyl radical (I{sup ·}), which is proposed to be a key intermediate in the reaction of pyridoxal-5′-phosphate dependent radical aminomutases. We have calculated the corresponding hyperfine coupling constants (HFCCs) for {sup 14}N and {sup 13}C of cyano group using several basis sets to help the characterization of 4′-cyanoI{sup ·}.

  7. 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

  8. 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

  9. 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

  10. 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 through…

  11. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: the roles of Galphaq, PLC-beta, IP3 and 5,6-epoxyeicosatrienoic acid.

    PubMed

    Muldowney, James A S; Painter, Corrie A; Sanders-Bush, Elaine; Brown, Nancy J; Vaughan, Douglas E

    2007-02-01

    The acute physiologic release of tissue-type plasminogen activator (t-PA) from the endothelium is critical for vascular homeostasis. This process is prostacyclin- and nitric oxide (NO)-independent in humans. It has been suggested that calcium signaling and endothelial-derived hyperpolarizing factors (EDHF) may play a role in t-PA release. G-protein-coupled receptor-dependent calcium signaling is typically Galphaq-dependent. EDHFs have been functionally defined and in various tissues are believed to be various regioisomers of the epoxyeicosatrienoic acids (EETs). We tested the hypothesis in vitro that thrombin-stimulated t-PA release from human microvascular endothelial cells (HMECs) is both Galphaq- and EDHF-dependent. Conditioned media was harvested following thrombin stimulation, and t-PA antigen was measured by ELISA. Thrombin-induced t-PA release was limited by a membrane-permeable Galphaq inhibitory peptide, the PLC-beta antagonist U73122, and the IP3 receptor antagonist 2-aminoethoxyphenylborane, while the Galphaq agonist Pasteurella toxin modestly induced t-PA release. The cytochrome P450 (CYP450) inhibitor, miconazole, and the arachidonic acid epoxygenase inhibitor MS-PPOH inhibited thrombin-stimulated t-PA release, while 5,6-EET-methyl ester stimulated t-PA release. The 5,6- and 14,15-EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid, inhibited t-PA release at the 100 microM concentration. However, thrombin-stimulated t-PA release was unaffected by the prostacyclin and NO inhibitors ASA and L-NAME, as well as the potassium channel inhibitors TEA, apamin and charybdotoxin. These studies suggest that thrombin-stimulated t-PA release is Galphaq-, PLC-beta-, IP3-, and 5,6-EET-dependent while being prostacyclin-, NO- and K+ channel-independent in HMECs. PMID:17264956

  12. Dimethyl and diethyl esters of 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carb-oxy-lic acid: a comparison.

    PubMed

    Alfonso, Montserrat; Stoeckli-Evans, Helen

    2016-02-01

    In dimethyl 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carboxyl-ate, C18H14N4O4, (I), and diethyl 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carboxyl-ate, C20H18N4O4, (II), the dimethyl and diethyl esters of 5,6-bis-(pyridin-2-yl)pyrazine-2,3-di-carb-oxy-lic acid, the orientation of the two pyridine rings differ. In (I), pyridine ring B is inclined to pyrazine ring A by 44.8 (2)° and the pyridine and pyrazine N atoms are trans to one another, while pyridine ring C is inclined to the pyrazine ring by 50.3 (2)°, with the pyridine and pyrazine N atoms cis to one another. In compound (II), the diethyl ester, which possesses twofold rotation symmetry, the pyridine ring is inclined to the pyrazine ring by 40.7 (1)°, with the pyridine and pyrazine N atoms trans to one another. In the crystal of (I), mol-ecules are linked by C-H⋯N hydrogen bonds, forming chains along [001]. The chains are linked by C-H⋯π inter-actions, forming a three-dimensional structure. In the crystal of (II), mol-ecules are linked via C-H⋯O hydrogen bonds, forming a three-dimensional framework. There are C-H⋯π inter-actions present within the framework. PMID:26958396

  13. 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. PMID:26092973

  14. Multicomponent Double Diels-Alder/Nazarov Tandem Cyclization of Symmetric Cross-Conjugated Diynones to Generate [6-5-6] Tricyclic Products.

    PubMed

    Carmichael, Rachael A; Chalifoux, Wesley A

    2016-06-20

    The construction of complex polycyclic terpenoid products in an efficient and step-economical manner using multicomponent and tandem processes is highly valuable. Herein, we report a tandem cyclization sequence that initiates with a multicomponent double Diels-Alder reaction of cross-conjugated diynones, followed by a Nazarov cyclization to efficiently produce [6-5-6] tricyclic products with excellent regio- and diastereoselectivity. This methodology generates five new carbon-carbon bonds, three rings, quaternary or vicinal quaternary carbons, and stereogenic centers in a one-pot reaction. PMID:27124516

  15. 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.

  16. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a citrus flavonoid, on protection against memory impairment and neuronal cell death in a global cerebral ischemia mouse model.

    PubMed

    Okuyama, Satoshi; Morita, Mayu; Miyoshi, Kazuhiro; Nishigawa, Yuki; Kaji, Miki; Sawamoto, Atsushi; Terugo, Tsukasa; Toyoda, Nobuki; Makihata, Nahomi; Amakura, Yoshiaki; Yoshimura, Morio; Nakajima, Mitsunari; Furukawa, Yoshiko

    2014-05-01

    The present study evaluated the effects of treatment with the citrus flavonoid, 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) on protection against memory impairment and neuronal death in a global cerebral ischemia mouse model. The results showed that HMF, administrated for three days immediately after ischemic surgery, protected against ischemia-induced memory dysfunction, rescued neuronal cell death in the CA1 cell layer, increased the production of BDNF, stimulated the autophosphorylation of CaMK II and suppressed microglial activation in the hippocampus. These results suggest that HMF has a neuroprotective effect after brain ischemia by inducing BDNF production and anti-inflammatory effects. PMID:24657445

  17. Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues

    PubMed Central

    Elagawany, Mohamed; Schmitt, Martine; Ghiaty, Adel; El-Etrawy, A. Sh.; Ibrahim, Mohamed A.; Bihel, Frédéric; Sbardelotto, Aline Borba; Pessoa, Cláudia; Nguyen, Tam Luong; Hamel, Ernest; Bourguignon, Jean Jacques

    2013-01-01

    Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDA-MB-435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity. PMID:23574386

  18. 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

  19. Synthesis, structure-activity relationships and biological evaluation of 4,5,6,7-tetrahydropyrazolopyrazines as metabotropic glutamate receptor 5 negative allosteric modulators.

    PubMed

    Hirose, Wataru; Kato, Yoshihiro; Yamamoto, Takayoshi; Kassai, Momoe; Takata, Makoto; Hayashi, Shun; Arai, Yukiyo; Imai, Satoki; Yoshida, Kohzo

    2016-08-15

    The design, synthesis and SAR studies of novel 4,5,6,7-tetrahydropyrazolopyrazines as metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) are presented in this letter. Starting from a HTS hit compound (1, IC50=477nM), optimization of various groups led to the synthesis of a potent mGluR5 NAM (32, IC50=75nM) with excellent rat PK profile and good brain penetration. This compound produced oral antidepressant-like effect in a mouse tale suspension model (MED: 30mg/kg). PMID:27432763

  20. Intestinal absorption and fecal excretion of 5,6 alpha-epoxy-5 alpha-cholesta-3 beta-ol by the male Wistar rat

    SciTech Connect

    Bascoul, J.; Domergue, N.; Mourot, J.; Debry, G.; Crastes de Paulet, A.

    1986-12-01

    The intestinal absorption of 5,6 alpha-epoxy-5 alpha-cholesta-3 beta-ol, an oxysterol formed by cholesterol autoxidation, has been evaluated in the male Wistar rat. Measurement of the /sup 14/C//sup 3/H ratio in the serum (by the method of Zilversmit and Hugues) and in the feces showed that a large proportion of the epoxide was absorbed. Epoxide clearance from the blood was very rapid, but its excretion in the stool continued for several days, corresponding to the fraction of the epoxide stored in the animal.

  1. A facile synthesis and fungicidal activities of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones

    PubMed Central

    Zheng, Ai-Hua; Ruan, Xu-Zhi

    2008-01-01

    Summary The aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates generated carbodiimides 4, which were reacted with alkylamines under mild conditions to give a series of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones 6 and 8 in satisfactory yield. Their structures were confirmed by 1H NMR, EI-MS, IR and elementary analysis, and compound 8c was further analyzed by single-crystal X-ray diffraction. The preliminary bioassays indicated that these compounds showed excellent fungicidal activities against six kinds of fungi. PMID:19190737

  2. 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.

  3. Lipophilic and hydrophilic esters of 4-acetyl-2-(2-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one as antihypertensive agents.

    PubMed

    Fogt, S W; Scozzie, J A; Heilman, R D; Powers, L J

    1980-12-01

    In an attempt to enhance the antihypertensive activity of 4-acetyl-2-(2-hydroxyethyl)-5,6-bis(4-chlorophenyl)-2H-pyridazin-3-one, 1, a series of lipophilic and hydrophilic esters was synthesized. These derivatives possessed increased lipid and aqueous solubility, respectively. The esters, in general, cause a larger blood-pressure drop than 1 when tested at high doses in the spontaneously hypertensive rat (SHR) model. At lower doses the antihypertensive activity is the same as with 1. PMID:7452699

  4. Effect of cordycepin(3'-deoxyadenosine) on excision repair of 5,6-dihydroxy-dihydrothymine-type products from the DNA of Micrococcus radiodurans

    SciTech Connect

    Patil, M.S.; Tundo, V.J.; Locher, S.E.; Hariharan, P.V.

    1983-07-01

    Cordycepin(3'-deoxyadenosine), a nucleoside analog, has been shown to enhance radiation-induced cell killing. In an effort to elucidate the possible mechanism for enhancement of cell killing, the effect of cordycepin on the excision repair of radiation-induced 5,6-dihydroxy-dihydrothymine-type (t') products from the DNA of wild type Micrococcus radiodurans was investigated. The capacity of M. radiodurans to excise nondimeric (t') products from its DNA was significantly impaired after cordycepin treatment. The results suggest that the increased radiation sensitivity of cordycepin-treated cells could be due to alterations in cellular processes that repair DNA damage.

  5. Isorecticular Synthesis of Dissectible Molecular Bamboo Tubes of Hexarhenium(I) Benzene-1,2,3,4,5,6-hexaolate Complexes.

    PubMed

    Tseng, Tien-Wen; Luo, Tzuoo-Tsair; Liao, Shi-Hao; Lu, Kai-Hsiang; Lu, Kuang-Lieh

    2016-07-11

    A family of bamboo-like metal-organic nanotubes consisting of in situ synthesized macromolecular blocks (MB) is reported. The MBs are composed of six fac-(CO)3 Re cores, one benzene-1,2,3,4,5,6-hexaolate plate, and six pyridine-derivative pillar ligands, which have a doubly tri-legged geometry and can be mutually assembled, piece by piece. This entire system is characterized as a simple but precise supramolecular complexation of these macromolecular blocks and further introduces an archetypal approach to systematically constructing a tunable form of dissectible molecular bamboo tubes. PMID:27126190

  6. Cleft Lip/Palate, Short Stature, and Developmental Delay in a Boy with a 5.6-Mb Interstitial Deletion Involving 10p15.3p14

    PubMed Central

    Gamba, Bruno F.; Rosenberg, Carla; Costa, Silvia; Richieri-Costa, Antonio; Ribeiro-Bicudo, Lucilene A.

    2015-01-01

    The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has been implicated in a few well-known human phenotypes, namely HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2 (DiGeorge syndrome 2), but a number of variable phenotypes have also been reported. Cleft lip/palate seems to be a very unusual finding within the clinical spectrum of patients with this deletion. Here, we report a male child born with short stature, cleft lip/palate, and feeding problems who was found to have a 5.6-Mb deletion at 10p15.3p14. PMID:25852446

  7. One-pot synthesis of tetrazole-1,2,5,6-tetrahydronicotinonitriles and cholinesterase inhibition: Probing the plausible reaction mechanism via computational studies.

    PubMed

    Hameed, Abdul; Zehra, Syeda Tazeen; Abbas, Saba; Nisa, Riffat Un; Mahmood, Tariq; Ayub, Khurshid; Al-Rashida, Mariya; Bajorath, Jürgen; Khan, Khalid Mohammed; Iqbal, Jamshed

    2016-04-01

    In the present study, one-pot synthesis of 1H-tetrazole linked 1,2,5,6-tetrahydronicotinonitriles under solvent-free conditions have been carried out in the presence of tetra-n-butyl ammonium fluoride trihydrated (TBAF) as catalyst and solvent. Computational studies have been conducted to elaborate two plausible mechanistic pathways of this one-pot reaction. Moreover, the synthesized compounds were screened for cholinesterases (acetylcholinesterase and butyrylcholinesterase) inhibition which are consider to be major malefactors of Alzheimer's disease (AD) to find lead compounds for further research in AD therapy. PMID:26851737

  8. 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

  9. Etude par spectrometrie infrarouge et Raman de la triméthyl-4,5,6 pyrimidone-2 et de son chlorhydrate. Complexation par les halogenures de potassium

    NASA Astrophysics Data System (ADS)

    Lautié, Alain; Picquenard, Eric; Ratovelomanana, Nicole

    The i.r. Raman spectra of crystalline 4,5,6-trimethyl 2-pyrimidone and seven deuterated derivatives have been investigated between 4000 and 180 cm -1. Aqueous and CHCl 3 solutions were also examined. An assignment for intramolecular fundamentals is given, as well as a distinction between the most characteristic of each methyl group. The methylation and protonation effects are discussed. Furthermore, a 1/1 adduct of this pyrimidone and potassium halides is observed and characterized; it contains a strong NH…X - hydrogen bond.

  10. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile.

    PubMed

    Fancelli, Daniele; Moll, Jürgen; Varasi, Mario; Bravo, Rodrigo; Artico, Roberta; Berta, Daniela; Bindi, Simona; Cameron, Alexander; Candiani, Ilaria; Cappella, Paolo; Carpinelli, Patrizia; Croci, Walter; Forte, Barbara; Giorgini, Maria Laura; Klapwijk, Jan; Marsiglio, Aurelio; Pesenti, Enrico; Rocchetti, Maurizio; Roletto, Fulvia; Severino, Dino; Soncini, Chiara; Storici, Paola; Tonani, Roberto; Zugnoni, Paola; Vianello, Paola

    2006-11-30

    The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development. PMID:17125279

  11. Synthesis of Novel 3-Aryl-N-Methyl-1,2,5,6-Tetrahydropyridine Derivatives by Suzuki coupling: As Acetyl Cholinesterase Inhibitors

    PubMed Central

    Prasad, S.B. Benaka; Kumar, Y.C. Sunil; Kumar, C.S. Ananda; Sadashiva, C.T; Vinaya, K; Rangappa, K.S

    2007-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder affecting the central nervous system, which is also associated with progressive loss of memory and cognition. The development of numerous structural classes of compounds with different pharmacological profile could be an evolving, promising therapeutic approach for the treatment of AD. Thus, providing a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of Acetylcholinesterase (AChE) inhibitors. In view of this, we have synthesized novel 3-aryl-N-methyl-1,2,5,6-tetrahydropyridine derivatives 5a-k by Suzuki coupling and screened the efficacy of these derivatives for their AChE inhibitor activity. PMID:19662135

  12. 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. PMID:26920809

  13. 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.

  14. Design, Synthesis and Biological Evaluation of 5-Oxo-1,4,5,6,7,8 Hexahydroquinoline Derivatives as Selective Cyclooxygenase-2 Inhibitors

    PubMed Central

    Zarghi, Afshin; Sabakhi, Iman; Topuzyan, Vigen; Hajimahdi, Zahra; Daraie, Bahram

    2014-01-01

    A group of regioisomeric 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives possessing a COX-2 SO2Me pharmacophore at the para position of the C-2 or C-4 phenyl ring, in conjunction with a C-4 or C-2 phenyl (4-H) or substituted-phenyl ring (4-F,4-Cl,4-Br,4-OMe,4-Me, 4-NO2), were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. These target 5-oxo-1,4,5,6,7,8 hexahydroquinolines were synthesized via a Hansch condensation reaction. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 7,8-dihydro- 7,7-dimethyl-2-(4-methoxyphenyl)-4-(4-(methylsulfonyl)phenyl)quinolin-5(1H,4H,6H)- one (9c) as a potent COX-2 inhibitor (IC50 = 0.17 M) with a high COX-2 selectivity index (S.I. = 97.6) comparable to the reference drug celecoxib (COX-2 IC50 = 0.05 mM; COX-2 S.I= 405). A molecular modeling study where 9c was docked in active site of COX-2 showed that the p-SO2Me substituent on the C-2 phenyl ring is inserted into the secondary COX-2 binding site. The structure activity data acquired indicate that the position of the COX-2 SO2Me pharmacophore and type of substituent are important for COX-2 inhibitory activity. PMID:24711830

  15. Structural reassignment, absolute configuration, and conformation of hypurticin, a highly flexible polyacyloxy-6-heptenyl-5,6-dihydro-2H-pyran-2-one.

    PubMed

    Mendoza-Espinoza, José Alberto; López-Vallejo, Fabian; Fragoso-Serrano, Mabel; Pereda-Miranda, Rogelio; Cerda-García-Rojas, Carlos M

    2009-04-01

    The structural reassignment, absolute configuration, and conformational behavior of the highly flexible natural product hypurticin (pectinolide E), 6S-[3'S,5'R,6'S-triacetoxy-1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (1), were ascertained by a molecular modeling protocol, which includes extensive conformational searching, geometry optimization by DFT B3LYP/DGDZVP calculations, and comparison between the theoretical (DFT) and experimental (1)H-(1)H NMR coupling constants. Hyptolide (2), a related cytotoxic 5,6-dihydro-2H-pyran-2-one that increased the S phase of the HeLa cell cycle, was employed as a reference substance to validate the theoretical protocol designed to characterize the 3D properties of compound 1. The related synthetic derivative, tri-O-acetyl-3,6-dideoxy-d-glucose diphenyldithioacetal (14), was prepared by a six-step reaction sequence starting from d-glucose and served as an enantiopure building block to reinforce the structural and configurational assignment of 1. This protocol proved to be an important tool for the structural characterization of highly flexible bioactive polyoxygenated natural products. PMID:19265396

  16. Sex differences in GABA(B)R-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex.

    PubMed

    Marron Fernandez de Velasco, Ezequiel; Hearing, Matthew; Xia, Zhilian; Victoria, Nicole C; Luján, Rafael; Wickman, Kevin

    2015-08-01

    The medial prefrontal cortex (mPFC) has been implicated in multiple disorders characterized by clear sex differences, including schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, and drug addiction. These sex differences likely represent underlying differences in connectivity and/or the balance of neuronal excitability within the mPFC. Recently, we demonstrated that signaling via the metabotropic γ-aminobutyric acid receptor (GABABR) and G protein-gated inwardly-rectifying K(+) (GIRK/Kir3) channels modulates the excitability of the key output neurons of the mPFC, the layer 5/6 pyramidal neurons. Here, we report a sex difference in the GABABR-GIRK signaling pathway in these neurons. Specifically, GABABR-dependent GIRK currents recorded in the prelimbic region of the mPFC were larger in adolescent male mice than in female counterparts. Interestingly, this sex difference was not observed in layer 5/6 pyramidal neurons of the adjacent infralimbic cortex, nor was it seen in young adult mice. The sex difference in GABABR-GIRK signaling is not attributable to different expression levels of signaling pathway components, but rather to a phosphorylation-dependent trafficking mechanism. Thus, sex differences related to some diseases associated with altered mPFC function may be explained in part by sex differences in GIRK-dependent signaling in mPFC pyramidal neurons. PMID:25843643

  17. X-ray Mapping in Heterocyclic Design: XIV. Tricyclic Heterocycles Based on 2-Oxo-1,2,5,6,7,8-Hexahydroquinoline-3-Carbonitrile

    SciTech Connect

    Mazina, O.S.; Rybakov, V.B.; Chernyshev, V.V.; Babaev, E.V.; Aslanov, L.A.

    2004-11-01

    The structures of four compounds are studied using single-crystal X-ray diffraction: 1-[2-(4-chlorophenyl)-2-oxoethyl]-2-oxo-1,2,5,6,7,8-hexahydroquinoline -3-carbonitrile [a = 4.908(4) A, b = 11.644(10) A, c = 13.587(2) A, {beta} = 94.31(5) deg., Z = 2, space group P2{sub 1}]; 2-[2-(4-chlorophenyl)-2-oxoethoxy]-5,6,7,8-tetrahydroquinoline -3-carbonitrile [a = 7.6142(8) A, b = 14.778(2) A, c = 14.132(2) A, {beta} = 100.38(1) deg., Z = 4, space group P2{sub 1}/c]; 4-(aminocarbonyl)-2-(chlorophenyl)-6,7,8,9-tetrahydro[1.3]oxazolo[3,2-a] quinolin-3-ium perchlorate [a = 5.589(7) A, b = 24.724(15) A, c = 13.727(5) A, {beta} = 97.66(9) deg., Z = 4, space group P2{sub 1}/n]; and (3-amino-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-2-yl)-(4-chlorophenyl) methanone [a = 7.150(2) A, b = 7.4288(10) A, c = 15.314(3) A, {alpha} = 98.030(10) deg., {beta} = 99.21(2) deg., {gamma} = 105.34(2) deg., Z = 2, space group P1-bar]. The structures are solved by direct methods and refined by the full-matrix least-squares procedure in the anisotropic approximation to R = 0.0728, 0.0439, 0.1228, and 0.0541, respectively. The structure of 1-(4-chlorophenyl)-4-piperidin-1-yl-8,9-dihydro-7H-pyrrolo[3.2.1-ij] quinoline-5-carboxamide [a = 23.9895(9) A, b = 5.1557(3) A, c = 17.0959(9) A, {beta} = 106.43 deg., Z = 4, space group P{sub 1}/c] is investigated by X-ray powder diffraction. This structure is solved using the grid search procedure and refined by the Rietveld method to R{sub wp} = 0.0773, R{sub exp} = 0.0540, R{sub p} = 0.0585, R{sub b} = 0.1107, and {chi}{sup 2} = 1.78.

  18. Extension of TFTR operations to higher toroidal field levels

    SciTech Connect

    Woolley, R.D.

    1995-12-31

    For the past year, TFTR has sometimes operated at extended toroidal field (TF) levels. The extension to 5.6 Tesla (79 kA) was crucial for TFTR`s November 1994 10.7 MW DT fusion power record. The extension to 6.0 Tesla (85 kA) was commissioned on 9 September 1995. There are several reasons that one could expect the TF coils to survive the higher stresses that develop at higher fields. They were designed to operate at 5.2 Tesla with a vertical field of 0.5 Tesla, whereas the actual vertical field needed for the plasma does not exceed 0.35 Tesla. Their design specification explicitly required they survive some pulses at 6.0 Tesla. TF coil mechanical analysis computer models available during coil design were crude, leading to conservative design. And design analyses also had to consider worst-case misoperations that TFTR`s real time Coil Protection Calculators (CPCs) now positively prevent from occurring.

  19. Onset of Time-Dependent 3-D spherical Mantle Convection using a Radial Basis Function-Pseudospectral Method ; Spectral-Finite Volume ; Spectral Higher-Order Finite- Difference Methods

    NASA Astrophysics Data System (ADS)

    Wright, G.; Flyer, N.; Yuen, D. A.; Monnereau, M.; Zhang, S.; Wang, S. M.

    2009-05-01

    Many numerical methods, such as finite-differences, finite-volume, their yin-yang variants, finite-elements and spectral methods have been employed to study 3-D mantle convection. All have their own strengths, but also serious weaknesses. Spectrally accurate methods do not practically allow for node refinement and often involve cumbersome algebra while finite difference, volume, or element methods are generally low-order, adding excessive numerical diffusion to the model. For the 3-D mantle convection problem, we have introduced a new mesh-free approach, using radial basis functions (RBF). This method has the advantage of being algorithmic simple, spectrally accurate for arbitrary node layouts in multi-dimensions and naturally allows for node-refinement. One virtue of the RBF scheme allows the user to use a simple Cartesian geometry, while implementing the required boundary conditions for the temperature, velocities and stress components on a spherical surface at both the planetary surface and the core-mantle boundary. We have studied time- dependent mantle convection, using both a RBF-pseudospectral code and a code which uses spherical- harmonics in the angular direction and second-order finite volume in the radial direction. We have employed a third code , which uses spherical harmonics and higher-order finite-difference method a la Fornberg in the radial coordinate.We first focus on the onset of time-dependence at Rayleigh number Ra of 70,000. We follow the development of stronger time-dependence to a Ra of one million, using high enough resolution with 120 to 200 points in the radial direction and 128 to 256 spherical harmonics.

  20. Studies of hydrogen embrittlement and stress-corrosion cracking in an aluminum-zinc-magnesium alloy. [5. 6 Zn - 2. 6 Mg

    SciTech Connect

    Ciaraldi, S.W.; Nelson, J.L.; Yeske, R.A.; Pugh, E.N.

    1980-01-01

    Tensile tests have been carried out on a high-purity A1-5.6 Zn-2.6 Mg alloy hydrogenated by exposure to moist air. Results indicate that internal hydrogen embrittlement occurs by the formation and rupture of a stress-induced hydride at the grain boundaries. The hydride, identified by electron diffraction as A1H/sub 3/, is shown to be unstable in laboratory air, reverting to aluminum. The hydride phase was not detected in specimens failed by SCC, despite evidence that hydrogen is transported ahead of advancing stress-corrosion cracks, and this leads to the possibility that a basically different mechanism may be responsible for SCC in this alloy.

  1. Trinuclear nickel(II) complex through a 2,3,5,6-tetrakis(2-pyridyl)pyrazine ligand with a linear exchange pathway.

    PubMed

    Callejo, Lorena M; Madariaga, Gotzon; Lezama, Luis; Fidalgo, Luz; De la Pinta, Noelia; Cortés, Roberto

    2010-06-21

    The compound [Ni(3)(tppz)(2)(NCS)(2)(H(2)O)(4)](NO(3))(4).4H(2)O [tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine and NCS = thiocyanate ligand] consists of trimeric units, where the three Ni(II) cations are linked by two bis-tridentate tppz ligands. This compound crystallizes in the monoclinic space group C2/c, with Z = 4, a = 25.1116(12) A, b = 10.8127(5) A, c = 25.2294(13) A, and beta = 116.856(5) degrees . The crystal structure is in good agreement with the antiferromagnetic interactions because of unidirectional coupling through the tppz ligands. PMID:20507126

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

    PubMed

    Liu, Meiyou; Park, Jisoo; Wu, Xiaoxiao; Li, Yuwen; Tran, Quangdon; Mun, Kisun; Lee, Yongjin; Hur, Gang Min; Wen, Aidong; Park, Jongsun

    2015-10-01

    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. H2O

  3. 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]. PMID:26870556

  4. Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

    PubMed

    Liao, Shixian; Deng, Hui; Huang, Shengbin; Yang, Jingyuan; Wang, Siqian; Yin, Baodi; Zheng, Tieli; Zhang, Dafeng; Liu, Jinsong; Gao, Guohui; Ma, Jianfeng; Deng, Zhennan

    2015-04-01

    A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Aβ) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced Aβ1-42 aggregation with inhibition ratio of 33.8% at 25 μM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD. PMID:25724825

  5. Dichloro (1,10-phenanthroline-5,6-dione) palladium (II) complex supported by mesoporous silica SBA-15 as a photocatalyst for degradation of 2,4-dichlorophenol

    NASA Astrophysics Data System (ADS)

    Abolhosseini Sh., A.; Mahjoub, A. R.; Eslami-Moghadam, M.; Fakhri, H.

    2014-11-01

    A new photocatalyst, dichloro (1,10-phenanthroline-5,6-dione) palladium (II) complex supported on SBA-15 silica was synthesized by ship-in-a-bottle method. The products obtained were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Ultraviolet-Visible spectroscopy (UV-Vis), 1H NMR spectroscopy, N2 adsorption-desorption and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The band gap energy of the complex was determined by the diffuse reflectance spectroscopy (DRS) and density functional theory (DFT) calculation, indicating that it can be considered appropriate candidate for photocatalytic activity in the region of solar spectrum. The results indicated improved photocatalytic efficiency for the complex supported on SBA-15 silica compared to the pure complex. To improve photocatalytic activity, the effect of complex loading and optimal synthesis conditions were investigated.

  6. Experimental and DFT studies on the vibrational and electronic spectra of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Zhang, Fang; Ma, Kuirong; Tang, Guodong

    2013-03-01

    Vibrational and electronic spectral measurements were made for 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Optimized geometrical structure and harmonic vibrational frequencies were computed by DFT(B3LYP, CAMB3LYP, B3P86, M062X, mPW3PBE and PBE1PBE) using 6-311++G(d,p) basis set. Complete assignments of the observed spectra were proposed. The absorption spectra of the compound were computed both in gas-phase and in CH2Cl2 solution using TDCAMB3LYP/6-311++G(d,p) and PCM-TDCAMB3LYP/6-311++G(d,p) approaches, respectively, the calculated results provide a good description of positions of the bands maxima in the observed electronic spectrum.

  7. Structural analysis of three methyl N-phosphorylated 5,6-dihydroxy-2-azabicyclo[2.2.1]heptane-3-carboxylates

    NASA Astrophysics Data System (ADS)

    Sousa, Carlos A. D.; Vale, M. Luísa C.; Rodríguez-Borges, José E.; Garcia-Mera, Xerardo

    2012-01-01

    Both exo and endo isomers of (±)-methyl N-diphenylphosphoryl-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate and (±)-methyl N-diphenylphosphoryloxy-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate were dihydroxylated with OsO 4. The unexpected formation of (±)-methyl 5,6-dihydroxy -N-diphenylphosphoryl-2-azabicyclo[2.2.1]heptane-3- endo-carboxylate from (±)-methyl N-diphenylphosphoryloxy-2-azabicyclo[2.2.1]hept-5-ene-3- endo-carboxylate is discussed based on NMR analyses and experimental observations. The two N-diphenylphosphoryl dihydroxybicycles are analyzed in terms of their crystalline structure by X-ray crystallography.

  8. Early termination of heterogeneous nuclear RNA transcripts in mammalian cells: accentuation by 5,6-dichloro 1-beta-D-ribofuranosylbenzimidazole.

    PubMed Central

    Tamm, I; Kikuchi, T

    1979-01-01

    Labeling of RNA in isolated HeLa cell nuclei in vitro reveals an abundance of short RNA chains made by RNA polymerase II. These short chains were initiated prior to isolation of the nuclei. The short abundant chains are increased in amount in nuclei isolated from cells treated with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Kinetic evidence indicates that the bulk of the putative heterogeneous nuclear RNA (hnRNA) precursor molecules that are terminated early in vivo are terminated approximately 100-300 nucleotides from sites of initiation. DRB increases the frequency of early termination, but there is a fraction of hnRNA precursor molecules whose elongation is not affected by DRB. Heparin is useful in studies of hnRNA transcription in isolated nuclei because it enhances chain elongation. Images PMID:293679

  9. Conformation of gramicidin A in Triton X-100 micelles from CD and FTIR data: a clean example of antiparallel double β5.6 helix formation.

    PubMed

    Sychev, Sergei V; Barsukov, Leonid I; Ivanov, Vadim T

    2013-07-01

    The linear peptide gramicidin A (gA) forms prototypical ion channels specific for monovalent cations and has been extensively used to study the organization and dynamics of membrane channels. This polymorphic peptide can adopt two different types of structures, the helical dimer β6.3 ('channel state') and the double helical structure with two intertwined monomers. The structure of gA in micelles of detergent Triton X-100 has been studied using CD, Fourier transform infrared, and fluorescence spectroscopy. The results obtained demonstrate that only one thermodynamically stable gA structure, the antiparallel left-handed double helix β5.6, is formed in this membrane-mimetic environment. The position of the tryptophan fluorescence maximum at 332 nm is the same as that in phospholipid membranes. The causative factors governing the double helix formation in the micellar medium are discussed on the basis of known physicochemical properties of Triton X-100. PMID:23712944

  10. 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. PMID:27255179

  11. 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

    2002-03-01

    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). PMID:11863996

  12. 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.

  13. Modelling the optical constants of SixGe1-x alloys in the range 1.7-5.6 eV

    NASA Astrophysics Data System (ADS)

    Djurisic, Aleksandra B.; Li, E. Herbert

    2001-02-01

    Optical constants of SixGe1-x alloys are modelled over the spectral range from 0.7 eV to 5.6 eV for all compositions 0≤x≤1. The employed model is the modified Adachi's model, which utilizes variable line broadening instead of the conventional Lorentzian one. The model takes into account transitions at the indirect band gap Egid, and critical points E0, E0 + Δ0, E1, E1 + Δ1, E0', E2(X), and E2(Σ). Excitonic effects are not considered. The model parameters are determined using a global optimization routine, namely an acceptance-probability-controlled simulated annealing algorithm. Excellent agreement with the experimental data is obtained in the entire investigated energy and composition ranges. The obtained relative root mean square errors are below 4.5% and 6.5% for the real and imaginary parts of the index of refraction, respectively.

  14. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug.

    PubMed

    Kuwano, Keiichi; Hashino, Asami; Asaki, Tetsuo; Hamamoto, Taisuke; Yamada, Tetsuhiro; Okubo, Kaori; Kuwabara, Kenji

    2007-09-01

    Prostacyclin (PGI(2)) and its analogs are useful for the treatment of various vascular disorders, but their half-lives are too short for widespread clinical application. To overcome this drawback, we have synthesized a novel diphenylpyrazine derivative, 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), a prodrug of the active form [4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]acetic acid (MRE-269). NS-304 is an orally available and potent agonist for the PGI(2) receptor (IP receptor). The inhibition constant (K(i)) of MRE-269 for the human IP receptor was 20 nM; in contrast, the K(i) values for other prostanoid receptors were >2.6 microM. MRE-269 was therefore a highly selective agonist for the IP receptor. The plasma concentrations of MRE-269 remained near peak levels for more than 8 h after oral administration of NS-304 to rats and dogs, and NS-304 increased femoral skin blood flow in rats in a long-lasting manner without affecting the hemodynamics. These findings indicate that NS-304 acts as a long-acting IP receptor agonist in vivo. The continuous vasodilation evoked by NS-304 was not attenuated by repeated treatment, indicating that NS-304 is unlikely to cause severe desensitization of the IP receptor in rats. Moreover, a microdose pharmacokinetic study in which NS-304 was orally administered to healthy male volunteers showed conversion of NS-304 to MRE-269 and a long plasma elimination half-life for MRE-269 (7.9 h). In conclusion, NS-304 is an orally available and long-acting IP receptor agonist prodrug, and its active form, MRE-269, is highly selective for the IP receptor. Therefore, NS-304 is a promising drug candidate for various vascular diseases, especially pulmonary arterial hypertension and arteriosclerosis obliterans. PMID:17545310

  15. 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

  16. 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.

  17. 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

  18. The Increase in Phosphorylation Levels of Serine Residues of Protein HSP70 during Holding Time at 17°C Is Concomitant with a Higher Cryotolerance of Boar Spermatozoa

    PubMed Central

    Yeste, Marc; Estrada, Efrén; Rivera del Álamo, Maria-Montserat; Bonet, Sergi; Rigau, Teresa; Rodríguez-Gil, Joan-Enric

    2014-01-01

    Boar-sperm cryopreservation is not usually performed immediately after semen collection, but rather a holding time (HT) of 4 h–30 h at 17°C is spent before starting this procedure. Taking this into account, the aim of this study was to go further in-depth into the mechanisms underlying the improving effects of HT at 17°C on boar-sperm cryotolerance by evaluating the effects of two different HTs (3 h and 24 h) on overall boar-sperm function and survival before and after cryopreservation. Given that phospho/dephosphorylation mechanisms are of utmost importance in the overall regulation of sperm function, the phosphorylation levels of serine residues (pSer) in 30 different sperm proteins after a 3 h- or 24 h-HT period were also assessed. We found that a HT of 24 h contributed to a higher sperm resistance to freeze-thawing procedures, whereas mini-array protein analyses showed that a HT of 24 h induced a significant (P<0.05) increase in pSer (from 100.0±1.8 arbitrary units in HT 3 h to 150.2±5.1 arbitrary units in HT 24 h) of HSP70 and, to a lesser extent, in protein kinases GSK3 and total TRK and in the cell-cycle regulatory protein CDC2/CDK1. In the case of HSP70, this increase was confirmed through immunoprecipation analyses. Principal component and multiple regression analyses indicated that a component explaining a percentage of variance higher than 50% in sperm cryotolerance was significantly correlated with pSer levels in HSP70. In addition, from all the parameters evaluated before freeze-thawing, only pSer levels in HSP70 resulted to be able to predict sperm cryotolerance. In conclusion, our results suggest that boar spermatozoa modulate its function during HT, at least partially, by changes in pSer levels of proteins like HSP70, and this is related to a higher cryotolerance. PMID:24603527

  19. The increase in phosphorylation levels of serine residues of protein HSP70 during holding time at 17°C is concomitant with a higher cryotolerance of boar spermatozoa.

    PubMed

    Yeste, Marc; Estrada, Efrén; Rivera Del Álamo, Maria-Montserat; Bonet, Sergi; Rigau, Teresa; Rodríguez-Gil, Joan-Enric

    2014-01-01

    Boar-sperm cryopreservation is not usually performed immediately after semen collection, but rather a holding time (HT) of 4 h-30 h at 17°C is spent before starting this procedure. Taking this into account, the aim of this study was to go further in-depth into the mechanisms underlying the improving effects of HT at 17°C on boar-sperm cryotolerance by evaluating the effects of two different HTs (3 h and 24 h) on overall boar-sperm function and survival before and after cryopreservation. Given that phospho/dephosphorylation mechanisms are of utmost importance in the overall regulation of sperm function, the phosphorylation levels of serine residues (pSer) in 30 different sperm proteins after a 3 h- or 24 h-HT period were also assessed. We found that a HT of 24 h contributed to a higher sperm resistance to freeze-thawing procedures, whereas mini-array protein analyses showed that a HT of 24 h induced a significant (P<0.05) increase in pSer (from 100.0±1.8 arbitrary units in HT 3 h to 150.2±5.1 arbitrary units in HT 24 h) of HSP70 and, to a lesser extent, in protein kinases GSK3 and total TRK and in the cell-cycle regulatory protein CDC2/CDK1. In the case of HSP70, this increase was confirmed through immunoprecipation analyses. Principal component and multiple regression analyses indicated that a component explaining a percentage of variance higher than 50% in sperm cryotolerance was significantly correlated with pSer levels in HSP70. In addition, from all the parameters evaluated before freeze-thawing, only pSer levels in HSP70 resulted to be able to predict sperm cryotolerance. In conclusion, our results suggest that boar spermatozoa modulate its function during HT, at least partially, by changes in pSer levels of proteins like HSP70, and this is related to a higher cryotolerance. PMID:24603527

  20. Higher Education Exchange, 2014

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2014-01-01

    Research shows that not only does higher education not see the public; when the public, in turn, looks at higher education, it sees mostly malaise, inefficiencies, expense, and unfulfilled promises. Yet, the contributors to this issue of the "Higher Education Exchange" tell of bright spots in higher education where experiments in working…