1,088 research outputs found

    Openings of the rat recombinant alpha1 homomeric glycine receptor as a function of the number of sgonist molecules bound

    No full text
    The functional properties of rat homomeric {alpha}1 glycine receptors were investigated using whole-cell and outside-out recording from human embryonic kidney cells transfected with rat {alpha}1 subunit cDNA. Whole-cell dose-response curves gave EC50 estimates between 30 and 120 µM and a Hill slope of ~3.3. Single channel recordings were obtained by steady-state application of glycine (0.3, 1, or 10 µM) to outside-out patches. Single channel conductances were mostly 60–90 pS, but smaller conductances of ~40 pS were also seen (10% of the events) with a relative frequency that did not depend on agonist concentration. The time constants of the apparent open time distributions did not vary with agonist concentration, but short events were more frequent at low glycine concentrations. There was also evidence of a previously missed short-lived open state that was more common at lower glycine concentrations. The time constants for the different components of the burst length distributions were found to have similar values at different concentrations. Nevertheless, the mean burst length increased with increasing glycine. This was because the relative area of each burst-length component was concentration dependent and short bursts were favored at lower glycine concentrations. Durations of adjacent open and shut times were found to be strongly (negatively) correlated. Additionally, long bursts were made up of longer than average openings separated by short gaps, whereas short bursts usually consisted of single isolated short openings. The most plausible explanation for these findings is that long bursts are generated when a higher proportion of the five potential agonist binding sites on the receptor is occupied by glycine. On the basis of the concentration dependence and the intraburst structure we provide a preliminary kinetic scheme for the activation of the homomeric glycine receptor, in which any number of glycine molecules from one to five can open the channel, although not with equal efficiency

    Studies of NMDA receptor function and stoichiometry with truncated and tandem subunits

    No full text
    The subunits that compose eukaryotic glutamate ion channel receptors have three transmembrane domains (TMs) and terminate with intracellular tails that are important for controlling channel expression and localization. Truncation of NMDA receptor subunits before the final TM showed that this TM and intracellular tail region are necessary to form functional channels. However, it is shown here that these truncated subunits may be partially rescued by coexpressing the final TM and tail as a separate protein. The whole-cell currents so produced are somewhat lower than with full-length subunits, and they do not show the sag characteristic of currents from channels containing NR1 and NR2A subunits in the continued presence of an agonist. In addition, these truncated subunits were joined to full-length subunits to generate tandems. The functional expression of these tandems confirmed the tetrameric structure of NMDA receptors and also suggested that the subunits making up NMDA receptors are arranged as a dimer of dimers in the receptors with a 1-1-2-2 orientation of the subunits in the channel, and not in an alternating pattern of subunits around the pore. These results may redirect future studies into the mechanism of binding and gating in these receptors toward schemes including dimers, and may also be relevant to studies of glutamate receptor ion channels in general

    Pressure groups and government policy on education, 1800 - 1839.

    No full text
    This study examines the roles of the principal groups and individuals, who, during the years 1800-1839, promoted the education of the poor and pressurised governments with the notion that the state ought to ac ept responsibility for the formation of a nationa1 system. Their m tives were primarily religious, philanthropic or political with a degree of self-interest in the desire to preserve order in society. The religious interests are examined mainly through the work of the British and Foreign Sch ol Society, which served the Dissenter traditi ns, and the Nati nal S ciety which defended the prerogative of the Establi h d Church t superintend the education of the people. The tilitarians and Radicals were imp rtant for the practica1 expression f their philos phical and political ideas led them to make a considerable c ntributi n to the provision schools. They also had the inspiration and organising ability of Jam s Mill and Francis Place. The ideas of Robert Owen are considered because he was a pressure figure for a few years, but his work also sowed the seeds of Co-operation and w rking-cla s movements, which made an impact during the 1830's. As the populati n slowly improved in standard of learning, the development of Mechanics' Institutes, the Society for the Difflision of Useful Knowledge and the foundation of University College are viewed as part of a strategy for the general promotion of adult education1 The dominant personality of Henry Brougham is evident in much of this study. He instituted the Charity Commissions in 1819, was spokesman (iv) for education in Parliament for many years, anj was a link between the different groups because of his involvement in so many. During the 1830's the new science of statistics emerged and the Statistical Societies were important for their presentation of data on education1 The existence of a National Board of Education in Ireland after 1831 placed the province ahead of England and the influences from this experiment, mediated to Parliament by Thomas Wyse and others, all helped to pressurise the governments of the day, whose policy had been to encourage voluntary effort and to avoid the imposition of central administrative control

    How to Impose Microscopic Reversibility in Complex Reaction Mechanisms

    No full text
    Most, but not all, ion channels appear to obey the law of microscopic reversibility (or detailed balance). During the fitting of reaction mechanisms it is therefore often required that cycles in the mechanism should obey microscopic reversibility at all times. In complex reaction mechanisms, especially those that contain cubic arrangements of states, it may not be obvious how to achieve this. Three general methods for imposing microscopic reversibility are described. The first method works by setting the ‘obvious’ four-state cycles in the correct order. The second method, based on the idea of a spanning tree, works by finding independent cycles (which will often have more than four states) such that the order in which they are set does not matter. The third method uses linear algebra to solve for constrained rates

    Jüri Okas’ ‘specific objects’: diverging discourses in Estonian Art in the 1970s.

    No full text
    Previously in the University eprints HAIRST pilot service at http://eprints.st-andrews.ac.uk/archive/00000367/Article 3 of 6 in issue devoted to the visual culture of the Scandinavian and Baltic region.This article will look at the early works of Estonian architect and artist Jüri Okas and will try to work between diverging languages and interpretations, reading works by Okas against the background of Anglo-american conceptualism and minimalism of the same period. The first part of the paper will analyse a print by Jüri Okas that paraphrases works by the American artist Donald Judd and will try to show how Okas’ concept of minimalism differed from the Western one and the reasons behind it. The second part of the paper will focus on a conceptual book by Jüri Okas, consisting of a series of photographs of everyday and banal architectural objects, and compare it to Rober Venturi’s book on Complexity and Contradiction in Architecture. Finally, a comparison will be made with works of Robert Smithson in the context of concepts of waste, excess and the remainders of industrial civilisationPostprin

    Fig. 5. Total ubiquinone-9 in 3-O-glycosylation of kaempferol restricts the supply of the benzenoid precursor of ubiquinone (Coenzyme Q) in Arabidopsis thaliana

    No full text
    Fig. 5. Total ubiquinone-9 content in the rosette leaves of wild-type, ugt78d2, f3′h, and f3′h/ugt78d2 plants. Plants were grown on soil in 16-h days (110 μE m 2 s 1) at 22 ◦C for 3 weeks. Data represent the means of 7–8 biological replicates ±SE. P values from an analysis of variance between each mutant and the wild-type reference are indicated above the bars. The asterisk indicates significant differences from the wild type as determined by variance analysis (P <α = 0.1).Published as part of Soubeyrand, Eric, Latimer, Scott, Bernert, Ann C., Keene, Shea A., Johnson, Timothy S., Shin, Doosan, Block, Anna K., Colquhoun, Thomas A., Sch, Anton R., affner, Kim, Jeongim & Basset, Gilles J., 2021, 3-O-glycosylation of kaempferol restricts the supply of the benzenoid precursor of ubiquinone (Coenzyme Q) in Arabidopsis thaliana, pp. 1-6 in Phytochemistry (112738) 186 on page 4, DOI: 10.1016/j.phytochem.2021.112738, http://zenodo.org/record/825843

    Single channel study of the spasmodic mutation α1A52S in recombinant rat glycine receptors

    No full text
    Inherited defects in glycine receptors lead to hyperekplexia, or startle disease. A mutant mouse, spasmodic, that has a startle phenotype, has a point mutation (A52S) in the glycine receptor α1 subunit. This mutation reduces the sensitivity of the receptor to glycine, but the mechanism by which this occurs is not known. We investigated the properties of A52S recombinant receptors by cell-attached patch clamp recording of single-channel currents elicited by 30 – 10000 μM glycine. We used heteromeric receptors, which resemble those found at adult inhibitory synapses. Activation mechanisms were fitted directly to single channel data using the HJCFIT method, which includes an exact correction for missed events. In common with wildtype receptors, only mechanisms with three binding sites and extra shut states could describe the observations. The most physically plausible of these, the ‘flip’ mechanism, suggests that pre-opening isomerisation to the flipped conformation that follows binding is less favoured in mutant than in wild-type receptors, and, especially, that the flipped conformation has a 100-fold lower affinity for glycine than in wildtype receptors. In contrast, the efficacy of the gating reaction was similar to that of wild-type heteromeric receptors. The reduction in affinity for the flipped conformation accounts for the reduction in apparent cooperativity seen in the mutant receptor (without having to postulate interaction between the binding sites) and it accounts for the increased EC50 for responses to glycine that is seen in mutant receptors. This mechanism also predicts accurately the faster decay of synaptic currents that is observed in spasmodic mice

    The adoption of deferred share unit plans for outside directors and shareholder wealth

    No full text
    Manuscript Type: Empirical Research Question-Issue: We examine the impact of the adoption of deferred share unit (DSU) plans for directors on a firm's stock market value. We also examine the differential response to plan and firm characteristics. Research Findings-Results: The sample comprises all firms within Canada's top 1,000 that adopted DSU plans between 1997 (first one) and 2005. Results show that adopters exhibit positive abnormal returns at the adoption announcements and that these vary in accordance with DSU attributes: Investors reward firms that adopt stricter standards. Findings also indicate a more positive reaction when firms are widely held, have higher levels of related directors, higher free cash flows, and are not cross-listed in the US. Theoretical-Implications: The paper adds to the scant literature on directors' compensation by examining a recent development in directors' pay; DSU plans having many distinguishing features that set them apart from stock options. Second, it investigates whether investors' reaction varies with DSU attributes. Third, the specificity of the Canadian settings allows an analysis of the reaction to DSU adoption given different ownership structures and stock market listing. Practial Implications: The positive stock market reaction to DSU adoption provides valid economic underpinnings to the current worldwide trend in director compensation toward the cancellation of stock option plans and their substitution by DSU. However, the adoption of DSU plans for directors does not add much value in settings where there is already good monitoring by a large shareholder, by a broader investor base or by the board. © 2008 Blackwell Publishing Ltd.Aerts W, 2007, CORP GOV, V15, P1301; Agrawal A, 1996, J FINANC QUANT ANAL, V31, P377, DOI 10.2307-2331397; Anderson RC, 2004, J ACCOUNT ECON, V37, P315, DOI 10.1016-j.jacceco.2004.01.004; BEATTY RP, 1994, ADMIN SCI QUART, V39, P313, DOI 10.2307-2393238; BEBCHUK L, 2007, 573 HARV LAW SCH; Bebchuk LA, 2002, U CHICAGO LAW REV, V69, P751, DOI 10.2307-1600632; Bedard J, 2004, AUDITING-J PRACT TH, V23, P13, DOI 10.2308-aud.2004.23.2.13; BELCREDI M, 2004, INT J DISCLOSURE GOV, V1, P171, DOI 10.1057-palgrave.jdg.2040022; Ben-Amar W, 2006, J BUS FINAN ACCOUNT, V33, P517, DOI 10.1111-j.1468-5957.2006.00613.x; Berle A., 1932, MODERN CORPORATION P; Bhagat S, 1999, BUS LAWYER, V54, P885; BOUMOSLEH A, 2005, DIRECTOR COMPENSATIO; *CAN COAL GOOD GOV, 2005, CORP GOV GUID BUILD; Claessens S, 2002, J FINANC, V57, P2741, DOI 10.1111-1540-6261.00511; Coffee JC, 1999, NORTHWEST U LAW REV, V93, P641; COLQUHOUN N, 2003, EXECUTIVE COMPENSATI; Core JE, 1999, J FINANC ECON, V51, P371, DOI 10.1016-S0304-405X(98)00058-0; Craighead J., 2004, CONT ACCOUNTING REV, V21, P369, DOI 10.1506-BPCX-D3FC-Y8VY-M541; Cronqvist H, 2003, J FINANC QUANT ANAL, V38, P695, DOI 10.2307-4126740; Dalton DR, 2001, BUS ETHICS Q, V11, P89, DOI 10.2307-3857871; Defond ML, 2004, J ACCOUNTING RES, V42, P269, DOI 10.1111-j.1475-679X.2004.00138.x; Denis D. K., 2001, REV FINANCIAL EC, V10, P191, DOI 10.1016-S1058-3300(01)00037-4; Doidge C, 2004, J FINANC ECON, V71, P205, DOI 10.1016-S0304-405X(03)00183-1; Doidge C, 2004, J FINANC ECON, V72, P519, DOI 10.1016-S0304-405X(03)00208-3; EISENHARDT KM, 1989, ACAD MANAGE REV, V14, P532, DOI 10.2307-258557; Elson C., 1996, SO METHODIST U LAW R, V50, P135; ELSON C, 1999, DIRECTORSHIP, V25, P3; Feltham G., 2001, REV ACCOUNT STUD, V6, P7, DOI 10.1023-A:1011377902967; Ferris SP, 2003, J FINANC, V58, P1087, DOI 10.1111-1540-6261.00559; Fich EM, 2005, J BUS, V78, P2229, DOI 10.1086-497048; FORGIE J, 1998, DEMYSTIFYING DSUS; GAVER JJ, 1992, ACCOUNT REV, V67, P172; Gerety M, 2001, FINANC MANAGE, V30, P45, DOI 10.2307-3666258; GRAY J, 2001, CANADIAN BUSINESS, V74, P40; Gul FA, 1997, J ACCOUNT ECON, V24, P219, DOI 10.1016-S0165-4101(98)00006-8; Hall B., 2003, J APPL CORPORATE FIN, V15, P21, DOI 10.1111-j.1745-6622.2003.tb00458.x; Hambrick DC, 2000, CALIF MANAGE REV, V42, P108; Hermalin BE, 1998, AM ECON REV, V88, P96; Hillman AJ, 2003, ACAD MANAGE REV, V28, P383; JENSEN MC, 1986, AM ECON REV, V76, P323; JENSEN MC, 1993, J FINANC, V48, P831, DOI 10.2307-2329018; JENSEN MC, 1976, J FINANC ECON, V3, P305, DOI 10.1016-0304-405X(76)90026-X; Klein A, 2002, J ACCOUNT ECON, V33, P375, DOI 10.1016-S0165-4101(02)00059-9; Kumar P., 2002, OPTIMAL INCENTIVE ST; KUMAR R, 1992, J FINANC QUANT ANAL, V27, P561, DOI 10.2307-2331140; La Porta R, 2002, J FINANC, V57, P1147, DOI 10.1111-1540-6261.00457; LEBLANC R, 2004, IVEY BUSINESS J ONLI; Lin S., 2003, J BUSINESS FINANCE A, V30, P351, DOI 10.1111-1468-5957.t01-1-00001; Lublin J. S., 2006, WALL STREET J; *MERC HUM RES CONS, 2004, PERSP DIR COMP CAN; MILLIRON J, 2000, BOARD DIRECTOR INCEN; MORCK R, 1989, AM ECON REV, V79, P842; Officer MS, 2003, J FINANC ECON, V69, P431, DOI 10.1016-S0304-405X(03)00119-3; OPLER T, 1993, J FINANC, V48, P1985, DOI 10.2307-2329077; Peasnell KV, 2005, J BUS FINAN ACCOUNT, V32, P1311, DOI 10.1111-j.0306-686X.2005.00630.x; Perry T, 2005, J BUS, V78, P1403, DOI 10.1086-430864; Reese WA, 2002, J FINANC ECON, V66, P65, DOI 10.1016-S0304-405X(02)00151-4; Roe M., 2003, POLITICAL DETERMINAN; RONALD D, 1998, BENEFITS Q, V14, P18; ROSENSTEIN S, 1990, J FINANC ECON, V26, P175, DOI 10.1016-0304-405X(90)90002-H; Ryan HE, 2004, J FINANC ECON, V73, P497, DOI 10.1016-j.jfineco.2003.11.002; Shivdasani A, 1999, J FINANC, V54, P1829, DOI 10.1111-0022-1082.00168; SHIVDASANI A, 1993, J ACCOUNT ECON, V16, P167, DOI 10.1016-0165-4101(93)90009-5; Shleifer A, 1997, J FINANC, V52, P737, DOI 10.2307-2329497; WEISBACH MS, 1988, J FINANC ECON, V20, P431, DOI 10.1016-0304-405X(88)90053-0; Westphal JD, 1997, ADMIN SCI QUART, V42, P366, DOI 10.2307-2393924; Westphal JD, 1998, ADMIN SCI QUART, V43, P127, DOI 10.2307-2393593; Yen T.-Y., 2007, J ECON BUS, V59, P380, DOI 10.1016-j.jeconbus.2007.04.003; Yermack D, 2004, J FINANC, V59, P2281, DOI 10.1111-j.1540-6261.2004.00699.x; Young M. N., 2003, SAM ADV MANAGE J, V68, P4; Zajac EJ, 2004, AM SOCIOL REV, V69, P43342

    A systematic review of interventions to increase the use of standardized outcome measures by rehabilitation professionals

    No full text
    Objective: To determine the types and effectiveness of interventions to increase the knowledge about, attitudes towards, and use of standardized outcome measures in rehabilitation professionals.&nbsp; Data Sources: An electronic search using Medline, EMBASE, PsycINFO, CINAHL, Ergonomics Abstracts, Sports Discus. The search is current to February 2016.&nbsp; Study Selection: All study designs testing interventions were included as were all provider and patient types. Two reviewers independently conducted a title and abstract review, followed by a full-text review.&nbsp; Data extraction: Two reviewers independently extracted a priori variables and used consensus for disagreements. Quality assessment was conducted using the Assessment of Quantitative Studies published by the Effective Public Health Practice Group.&nbsp; Data Synthesis: We identified 11 studies involving at least 1200 providers. Nine of the studies showed improvements in outcome measure use rates but only three of these studies used an experimental or quasi-experimental design. Eight of the studies used an educational approach in the intervention and three used audit and feedback. Poor intervention description and quality of studies limited recommendations.&nbsp; Conclusions: Increased attention to testing interventions focused on known barriers, matched to behavior change techniques, and with stronger designs is warranted
    corecore