Relating student perceptions of readiness to student success: A case study of a mathematics module.

This study correlates the readiness survey scores of bona fide first year university students with their success in a mathematically based first year module. It follows on the need for skilled individuals in the fields of Science and Technology that exists across the globe and is continually becoming the focus of educational institutions world-wide. Similarly, in South Africa, universities were instructed to increase their intake of students in the fields of Science and Technology so as to provide for the technology orientated needs of the country, as well as to increase participation of previously disadvantaged race groups in these fields. In response to this instruction, universities increased the number of students enrolled in Science and Technology fields by 23% in recent years. The challenge is now to ensure that these students exit the university with a suitable degree in the shortest possible time. Statistics published by the South African Council of Higher Education affirms the extent of this challenge faced by universities-only 51% of students enrolled in the fields of Science and Technology complete their 3-year undergraduate degrees, and some of them took as long as 6 years to complete the 3-year degrees. This still leaves 49% of students that either took more than 6 years to complete their degrees, or did not complete their degrees at all. The underlying cause(s) for these failures must be identified and addressed. As a starting point in this discussion, the questions that this study aim to answer are whether first year students are in fact as prepared for the challenges at university as they perceive themselves to be; and whether student readiness (or lack thereof) can be a root cause for the low throughput rates. This study determines how prepared first year students, at a leading South African university, perceive themselves to be for the demands of university and, specifically, how their perceptions of their readiness in different areas correlate with their academic success in a mathematically based module. The correlation is determined by analysing data gathered through a readiness survey that is completed by first year students at the beginning of the academic year, and their final mark in the mathematics based first year module. The survey is a standardised, self-evaluation tool originally developed by the University of Pretoria. It is also applied at the university where this study is conducted. The survey measures the preparedness of students in different areas and the empirical study shows that there is a statistically significant correlation between the perception of the students regarding their planning ability and the final mark obtained in the mathematics based module.

Characterization of a 5-HT1B receptor on CHO cells: functional responses in the absence of radioligand binding.

1. Chinese hamster ovary (CHO) cells have been reported to be devoid of 5-HT receptors and have frequently been used as hosts for the expression of cloned 5-HT receptors. Unexpectedly, 5-HT was found to induce profound inhibition of forskolin-stimulated cyclic AMP production in these cells and the aim of this study was to classify the 5-HT receptor involved. 2. In CHO(dhfr-) cells 5-HT was a potent agonist and caused 80-100% inhibition of forskolin stimulated cyclic AMP production. A study using several 5-HT1 receptor agonists revealed the following potencies (p[A50]): RU24969 (9.09 +/- 0.17) > 5-carboxamidotryptamine (8.86 +/- 0.20) > 5-HT (8.07 +/- 0.05) > CP-93,129 (7.74 +/- 0.10) > sumatriptan (5.93 +/- 0.04). All five agonists achieved a similar maximum effect. Irreversible receptor alkylation studies yielded a pKA estimate of 7.04 +/- 0.34 for 5-HT. 3. The 5-HT1A/1B antagonist, (+/-)-cyanopindolol (4-100 nM), caused parallel rightward shifts of the 5-HT concentration-effect curve with no change in asymptote. Schild analysis yielded a pKB estimate of 8.69 +/- 0.09 (Schild slope 1.13 +/- 0.10). (+/-)-Cyanopindolol actually behaved as a partial agonist with an intrinsic activity of 0.2-0.5 and a p[A50] of 8.55. 4. 5-HT (0.01-10 microM) also elicited a concentration-dependent increase in intracellular [Ca2+] in CHO(dhfr-) cells thus demonstrating that dual coupling is not a phenomenon restricted to systems in which there is overexpression of transfected receptors. 5. This agonist and antagonist profile is consistent with the presence of a 5-HT1B receptor. 8-OH-DPAT (1 microM) and renzapride (3 microM) were without effect on forskolin-stimulated cyclic AMP production and ketanserin (0.3 microM) did not antagonize the inhibition produced by 5-HT, thus excluding the involvement of 5-HT1A, 5-HT4, and 5-HT2 receptors. 6. The possibility that expression of a 5-HT1B receptor was associated with the dhfr- mutation was excluded since RU24969, 5-HT and CP-93,129 were also potent agonists in unmutated, CHO-K1 cells: p[A50] 9.03 +/- 0.03, 8.34 +/- 0.05, 7.69 +/- 0.07 respectively, and (+/-)-cyanopindolol (0.1 microM) shifted the 5-HT curve to the right and yielded a pA2 estimate of 8.70 +/- 0.06. 7. Little or no specific binding of [3H]-5-HT (0.1-200 nM) or of the high affinity ligand [125I]-iodocyanopindolol (0.01-3 nM) to CHO(dhfr-) cell membranes could be detected. 5-HT also failed to elicit any increase in the binding of [35S]-GTP gamma S to CHO membranes. 8. In conclusion, cultured CHO cells express 5-HT1B receptors which are negatively coupled to adenylyl cyclase and positively coupled to increases in intracellular calcium. The absence of radioligand binding was unexpected in view of the high potency of 5-HT and the partial agonist activity of the normally 'silent' competitive antagonist, (+/-)-cyanopindolol. This implies very efficient receptor-effector coupling of a low density of 5-HT1B receptors. Clearly, the absence of detectable radioligand binding cannot be assumed to mean the absence of receptors capable of eliciting a significant functional response.

Synthesis of Hexahydrocyclopentimidazol-2-(1H)-one derivatives displaying selective DP-receptor agonist properties.

The rationale for investigating conformationally restricted analogues of BW245C as DP-receptor ligands and the syntheses of three such racemic bicyclic imidazolidinone analogues are described. Compounds 7 (BW587C), 8 (BW480C85), and 9 (BW572C85) were found to be potent inhibitors of human platelet aggregation and selective DP-receptor agonists in washed platelet and jugular vein isolated tissue assays.

Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence.

1. Isolated rings of rabbit external jugular vein (RbJV) and rat thoracic aorta (RA) were used to study the effect of the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) on muscarinic and 5-hydroxytryptamine (5-HT) receptor-stimulated, endothelium-dependent vascular relaxations. 2. In RbJV relaxations produced by the endothelial 5-HT receptor agonist alpha-methyl-5-HT were potently and non-surmountably inhibited by L-NAME (10 microM), whereas acetylcholine relaxations in this tissue were unaffected by this concentration of inhibitor. By contrast, acetylcholine relaxations in RA were virtually abolished by 10 microM L-NAME. In each case an equivalent concentration of D-NAME was without effect on agonist-induced relaxations. 3. The different effect of L-NAME on acetylcholine relaxations in RbJV and RA was not due to muscarinic receptor differences. Affinity estimates for acetylcholine (pKA = 6.12 +/- 0.09; 6.09 +/- 0.08 respectively) and for 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP, pKB = 9.01 +2- 0.012; 9.24 +/- 0.16 respectively) indicated that the receptors in both tissues belong to the same M3 class. Tissue differences resulting from the release of a cyclo-oxygenase product or a glibenclamide-sensitive K(+)-channel-linked hyperpolarizing factor were also ruled out by selective inhibition of these pathways. 4. When phenoxybenzamine was used to reduce the efficacy of acetylcholine in RbJV so that it behaved as a partial agonist in this tissue, L-NAME (10 microM) now produced non-surmountable inhibition of relaxation responses. In untreated tissues the same concentration of L-NAME also profoundly inhibited responses produced by butyrylcholine and pilocarpine, both of which behave as partial agonists at the M3 receptor in RbJV. 5. A simple model was developed which describes the theoretical behaviour of receptor-stimulated synthesis and release of NO. The model predicts that competitive inhibition of NO formation results in parallel displacements of the agonist response curve in the case of high efficacy agonist, but right-shift with concomitant depression of the curve maximum in the case of low efficacy agonists. Simulations based on the model showed reasonable agreement with the experimental data. 6. It is concluded that analogues of L-arginine demonstrate tissue- and agonist-dependence in terms of their ability to inhibit receptor-mediated events involving the liberation of NO. This behaviour can reflect differences in agonist efficacy in the receptor systems being studied, a possibility that should be ruled out before apparent resistance to inhibition is taken as evidence for the involvement of heterogeneous endothelium-derived relaxing factors (EDRFs).

A comparative study of the prostanoid receptor profile of 9 alpha 11 beta-prostaglandin F2 and prostaglandin D2.

1. The aim of this study was to determine the receptor profile of 9 alpha 11 beta-prostaglandin F2 (PGF2) and compare it with that of its parent, prostaglandin D2 (PGD2). The experiments were designed to overcome the problems associated with the presence of multiple prostanoid receptor sub-types in most tissues; the lack of selective antagonists for each receptor means that conclusions regarding efficacy at FP and EP2 receptors must remain provisional. 2. At DP receptors in human platelets and rabbit jugular vein, PGD2 was a full agonist, p[A50] 7.02 +/- 0.09 and 6.60 +/- 0.12 respectively. 9 alpha 11 beta-PGF2 was approximately 30-60 fold less potent than PGD2. 3. 9 alpha 11 beta-PGF2 was a full agonist in the FP receptor containing preparation, cat iris sphincter (p [A50] 7.35 +/- 0.09) comparable in potency to PGD2 (p[A50] 7.15 +/- 0.19). Likewise the two prostanoids showed similar potency at the TP receptor in guinea-pig aorta (9 alpha 11 beta-PGF2 p[A50] 6.00 +/- 0.07; PGD2 6.24 +/- 0.08). 4. 9 alpha 11 beta-PGF2 and PGD2 had efficacy but low potency at EP1 receptors (guinea-pig oesophageal muscularis mucosa) and demonstrated 2000-3000 fold lower potency than PGE2 (p[A50] 8.35 +/- 0.09). Similarly, in the EP2 receptor-containing preparation, cat trachea, 9 alpha 11 beta-PGF2 was 3500 fold less potent and PGD2 700 fold less potent than PGE2 (p[A50] 8.06 +/- 0.26). 5. 9 alpha 11 beta-PGF2 and PGD2 (10 microM) were without affinity at the IP receptors on human platelets and had no agonist action in the EP3 receptor containing preparation, guinea-pig vas deferens. 6. 9 alpha 11 beta,-PGF2 is a major metabolite of PGD2 in vivo and this conversion clearly represents an inactivation step since 9 alpha 11 beta-PGF2 is of considerably lower potency than PGD2 at DP receptors. However, it is of similar potency to PGD2 at TP, FP, EP1 and EP2 receptors and it may, therefore, contribute to the biological effects which follow PGD2 administration or endogenous synthesis; its actions at these receptors are likely to be similar to those of PGD2 itself.

The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist.

1. BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti-aggregatory concentration-effect curves to BW 245C were displaced in a parallel manner. The shifts accorded with a Schild plot slope of unity and a pKB of 9.26. 2. Inhibition of platelet aggregation by prostaglandin D2 (PGD2) was antagonized with a similar potency, as were the relaxation effects of BW 245C and PGD2 in the rabbit jugular vein. BW A868C can, therefore, be classified as a DP-receptor antagonist. 3. Actions of BW A868C at other prostaglandin receptors (IP, EP1, EP2, TP and FP) were excluded at concentrations up to 1,000 times higher than the DP-receptor affinity. 4. Analyses of BW 245C- and PGD2-mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C. In rabbit jugular vein a resistant phase of agonism was detectable, indicating that both agonists exerted effects through another receptor (possibly EP2). Also, PGD2, in addition to its anti-aggregatory effect on platelets, demonstrated a pro-aggregatory action in the presence of BW A868C. 5. The contractile effects of PGD2 in guinea-pig tracheal strips were resistant to 10 microM BW A868C indicating that they were not mediated through DP-receptors. 6. To our knowledge this is the first account of a well-classified competitive antagonist at the DP-receptor. Its potency and selectivity make it an important new tool in prostanoid receptor classification and identification.