Cyclic nucleotide-gated channels: structural basis of ligand efficacy and allosteric modulation

Most working proteins, including metabolic enzymes, transcription regulators, and membrane receptors, transporters, and ion channels, share the property of allosteric coupling. The term 'allosteric' means that these proteins mediate indirect interactions between sites that are physically separated on the protein. In the example of ligand-gated ion channels, the binding of a suitable ligand elicits local conformational changes at the binding site, which are coupled to further conformational changes in regions distant from the binding site. The physical motions finally arrive at the site of biological activity: the ion-permeating pore. The conformational changes that lead from the ligand binding to the actual opening of the pore comprise 'gating'. In 1956, del Castillo and Katz suggested that the competition between different ligands at nicotinic acetylcholine receptors (nAChRs) could be explained by formation of an intermediate, ligand-bound, yet inactive state of the receptor, which separates the active state of the receptor from the initial binding of the ligand (del Castillo & Katz, 1957). This 'binding-then-gating', two-step model went beyond the then-prevailing drug-receptor model that assumes a single bimolecular binding reaction, and paralleled Stephenson's conceptual dichotomy of 'affinity' and 'efficacy' (Stephenson, 1956). In 1965 Monod, Wyman and Changeux presented a simple allosteric model (the MWC model) (Monod et al. 1965) that explained the cooperative binding of oxygen to haemoglobin; it was adopted as an important paradigm for ligand-gated channels soon after its initial formulation (Changeux et al. 1967; Karlin, 1967; Colquhoun, 1973)

Do Frictions Matter in the Labor Market? Accessions, Separations and Minimum Wage Effects

We measure labor market frictions using a strategy that bridges design-based and structural approaches: estimating an equilibrium search model using reduced-form minimum wage elasticities identified from border discontinuities and fitted with Bayesian and LIML methods. We begin by providing the first test of U.S. minimum wage effects on labor market flows and find negative effects on employment flows, but not levels. Separations and accessions fall among restaurants and teens, especially those with low tenure. Our estimated parameters of a search model with wage posting and heterogeneous workers and firms imply that frictions help explain minimum wage effects.minimum wage, labor market flows, monopsony, Bayesian estimation

The literary criticism of TS Eliot

Thesis (M.A.)--Boston University, 1942. This item was digitized by the Internet Archive

Relationship between change in condition of beef cows during the pasture season and performance of their calves to weaning

One hundred and fifty-five Angus cows were measured ultrasonically for fat thickness using a Branson Model 12 Sonoray and visually scored for condition in April and October of 1966. Least-squares analyses of the data collected were conducted, using as a dependent variable in each analysis one of the three calf traits observed and recorded at weaning, viz., average daily gain, type score and condition score. The inde-pendent variables included in the model were age of dam, sex of calf, change in dam\u27s fat thickness, squared change in dam\u27s fat thickness, and age of calf. Change in fat thickness, as well as the squared change in dam\u27s fat thickness, significantly affected weaning condition score but not weaning gain or weaning type score. The same analyses were conducted with change in dam\u27s condition score substituted for change in fat thick-ness. Although cow condition score was highly correlated with each of the two ultrasonic estimates of fat thickness (r = 0.70 and 0.67 in spring and fall data, respectively), change in cow condition score did not affect weaning average daily gain, type or condition score of calf. A proposed explanation is that cow condition score may be influenced by cow size such that variation in condition score did not reflect dif-ferences in fatness as accurately as did the variation in ultrasonically measured fat thickness. The findings suggest that, under conditions similar to those in this study, change in fat thickness of the dam in conjunction with a measure of calf fatness might be useful in partitioning increases in calf weight into gain due to growth and gain due to fattening

A Matrix Application to Systems of n Linear and Non-Linear Homogenous 1st Order Differential Equations

In recent years, matrices have become very useful in the study of differential equations. The aim of this paper is to demonstrate the application of matrices to the existence and uniqueness of solutions to systems of differential equations. This matrix theory will be applied to both the linear and non-linear homogeneous 1st order cases