Rates and Equilibria for a Photoisomerizable Antagonist at the Acetylcholine Receptor of Electrophorus Electroplaques

Voltage-jump and light-flash experiments have been performed on isolated Electrophorus electroplaques exposed simultaneously to nicotinic agonists and to the photoisomerizable compound 2,2'-bis-[α-(trimethylammonium)methyl]-azobenzene (2BQ). Dose-response curves are shifted to the right in a nearly parallel fashion by 2BQ, which suggests competitive antagonism; dose-ratio analyses show apparent dissociation constants of 0.3 and 1 µM for the cis and trans isomers, respectively. Flash-induced trans → cis concentration jumps produce the expected decrease in agonist-induced conductance; the time constant is several tens of milliseconds. From the concentration dependence of these rates, we conclude that the association and dissociation rate constants for the cis-2BQ-receptor binding are approximately ~ 10^8 M^(-1) s^(-1) and 60 s^(-1) at 20ºC; the Q_(10) is 3. Flash-induced cis → trans photoisomerizations produce molecular rearrangements of the ligand-receptor complex, but the resulting relaxations probably reflect the kinetics of buffered diffusion rather than of the interaction between trans-2BQ and the receptor. Antagonists seem to bind about an order of magnitude more slowly than agonists at nicotinic receptors

SB 104 - Carjacking, Fentanyl and Upskirting

The Act includes various amendments to Georgia’s criminal code. Three changes are most notable. First, the Act designates the offense of hijacking a motor vehicle as hijacking a motor vehicle in the first degree and creates the offense of hijacking a motor vehicle in the second degree. Second, the Act criminalizes the use of a device to film underneath or through an individual’s clothing. Lastly, the Act adds the drug Fentanyl and its various analogs to the list of controlled substances

A covalently bound photoisomerizable agonist. Comparison with reversibly bound agonists at electrophorus electroplaques

After disulphide bonds are reduced with dithiothreitol, trans-3-(alpha-bromomethyl)-3’-[alpha-(trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this “tethered agonist” shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 [mu]M carbachol. Voltage- jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 mu M carbachol and have the same voltage and temperature sensitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-Qbr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to “open-channel blockade” bu QX-222. Light-flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist, 3,3’,bis-[alpha-(trimethylammonium)methyl]azobenzene (Bis-Q): the conductance is increased by cis {arrow} trans photoisomerizations and decreased by trans {arrow} cis photoisomerizations. As with Bis-Q, ligh-flash relaxations have the same rate constant as voltage-jump relaxations. Receptors with tethered trans isomer. By comparing the agonist-induced conductance with the cis/tans ratio, we conclude that each channel’s activation is determined by the configuration of a single tethered QBr molecule. The QBr-induced conductance shows slow decreases (time constant, several hundred milliseconds), which can be partially reversed by flashes. The similarities suggest that the same rate-limiting step governs the opening and closing of channels for both reversible and tethered agonists. Therefore, this step is probably not the initial encounter between agonist and receptor molecules

Analysis of a 290-Year Net Accumulation Time Series from Mt. Logan, Yukon

A 102.5-m mechanically continuous firn and ice core sequence retrieved from the Northwest Col of Mt. Logan (latitude 60°30\u27N; longitude 140°35\u27W; site location 5340 m a.s.l.) in the Yukon Territory, Canada, has been analyzed continuously for stable isotopes, pH and liquid electrolytic conductivity. Specific sections of the core have been analyzed for total β-activity (0-22 m) and trace ion concentrations (across major volcanic events) in order to date the core. In the lower half of the core, nitrate and some other ionic species are used to identify annual increments except between AD 1693 and AD 1720 and between AD 1729 and AD 1735 where only average annual increments are given. Annual increments were converted to water equivalents, then corrected for ice flow thinning as well as for origin, since a significant net accumulation gradient exists across the borehole site. The time series was subjected to cross correlation analysis, using instrumental data for the last 80 years, and to spectral analyses, using a 250-year sequence

Two little girls in blue: waltz song

https://digitalcommons.ithaca.edu/sheetmusic/1073/thumbnail.jp

Consortium of Otolaryngology Journal Editors: Collegiality and Contributions

There is a new tradition in the otolaryngology publishing community that is unique to our specialty, so far as we know. Editors-in-Chief of otolaryngology journals in the United States, and intermittently some of our international colleagues such as the Editor of the Journal of Laryngology and Otology (England), sit down together twice a year to discuss topics of mutual interest, maintain lines of communication and friendships, and share perspectives on the evolution of otolaryngology—head and neck surgery and needs that our journals might help address. To establish these collegial, uninhibited, informative, and productive meetings, Dr Robert Ruben proposed the idea of a Consortium of Otolaryngology Journal Editors. During the consortium’s formative years, the organization was solidified and supported by Jonas Johnson who was Editor-in-Chief of Laryngoscope from 2003 to 2008 and whose journal funded our meetings. The editors have discussed many topics including standardization of terminology, duplicate publication and plagiarism, increasing physician interest and involvement in peer-review, peer-review education, new publication models and their implications for our colleagues, support for resident presentations at scientific meetings, innovations at individual journals that might prove useful for other journals, increasing international involvement in our journals, predatory journals, and other topics

And then there were four: a study of UK market concentration - causes, consequences and the scope for market adjustment

While concentration measures are a good indicator of market structure, the link with competitiveness is more complex than often assumed. In particular, the modern theory of industrial organisation makes no clear statement regarding the impact of concentration on competition - the focus of this paper is concentration and no inferences are made about competitive aspects of the market. The extent and nature of concentration within the UK listed company audit market as at April, 2002 and, pro forma, after the collapse of Andersen is documented and analysed in detail (by firm, market segment and industry sector). The largest four firms held 90 per cent of the market (based on audit fees) in 2002, rising to 96 per cent with the demise of Andersen. A single firm, Pricewaterhouse-Coopers, held 70 per cent or more of the share of six out of 38 industry sectors, with a share of 50 per cent up to 70 per cent in a further seven sectors. The provision of non-audit services (NAS) by incumbent auditors is also considered. As at April 2002, the average ratio of non-audit fees (paid to auditor) to audit fees was 208 per cent, and exceeded 300 per cent in seven sectors. It is likely, however, that disposals by firms of their management consultancy and outsource firms, combined with the impact of the Smith Report on audit committees will serve to reduce these ratios. Another finding is that audit firms with expertise in a particular sector appeared to earn significantly higher nonaudit fees from their audit clients in that sector. The paper thus provides a solid empirical basis for debate. The subsequent discussion considers the implications for companies and audit firms of the high level of concentration in the current regulatory climate, where no direct regulatory intervention is planned

The power of interdependence: Linking health systems, communities, and health professions educational programs to better meet the needs of patients and populations

Promoting optimal health outcomes for diverse patients and populations requires the acknowledgement and strengthening of interdependent relationships between health professions education programs, health systems, and the communities they serve. Educational programs must recognize their role as integral components of a larger system. Educators must strive to break down silos and synergize efforts to foster a health care workforce positioned for collaborative, equitable, community-oriented practice. Sharing interprofessional and interinstitutional strategies can foster wide propagation of educational innovation while accommodating local contexts. This paper outlines how member schools of the American Medical Association Accelerating Change in Medical Education Consortium leveraged interdependence to accomplish transformative innovations catalyzed by systems thinking and a community of innovation