A connectionist approach to making the predictability of English orthography explicit to at-risk beginning readers: evidence for alternative, effective strategies.

A case is made (and illustrated with empirical data with children) for connectionist models that are not only computationally explicit but also instructionally explicit. First-graders (N = 128) at the bottom of their classes in reading (average 11.5 percentile on nationally normed tests) participated in a 3-layer intervention. In the first layer, kept constant for all treatment groups, the alphabet principle was taught, making functional spelling units and alternations explicit. In the second layer, which varied systematically across treatment groups, children received different kinds of tutor modeling in learning a set of words of varying spelling-sound predictability, using different connections between printed and spoken words, singly or in combination. In the third layer, also kept constant, children read and discussed illustrated books. Over the 4-month, 24-lesson intervention, all 7 treatment groups in the second layer improved more in word-specific learning than a contact control group that received phonological and orthographic awareness training without explicit instruction on orthographic-phonological connections. Of these 7, only 3 kinds of explicit modeling (whole word, letter-phoneme, and combined whole word and letter-phoneme) resulted in greater transfer to untrained words than the contact control or the other 4 kinds of explicit modeling. Results are discussed in reference to the controversy over whether dual route or connectionist models best account for the acquisition of reading.

Discrete membrane arrays.

This review describes various methods for the attachment of phospholipid bilayers to solid supports. The simplest approach involves vesicle unrolling onto a surface that has been previously modified with a continuous self-assembled monolayer (SAM). The choice of a suitable SAM can lead to the formation of attached bilayers that have the desired biomimetic properties and are suitable for studying transmembrane proteins. However, there are intrinsic problems associated with this approach if one is interested in studying ion transport phenomena. In particular, the relatively low resistance values found for such bilayers do not permit studies of single ion channels. For such studies to be carried out the background leakage through the lipid film must be greatly reduced. In an attempt to reduce the problems of leakage we have formed patterned SAMs in which a blocking, hydrophobic, layer covers 90% of the electrode surface. The remaining portion of the surface, which is hydrophilic, supports the formation of a bilayer. This approach has led to an improvement in the quality of the bilayers formed but has still not provided bilayers with sufficiently high specific resistances to study single ion channels. Finally, we describe new approaches based on the formation of bilayers suspended over small apertures. These 'suspended' bilayers are similar in structure to those used in black lipid membrane experiments and give rise to highly blocking bilayer membranes. Unfortunately, this approach requires the use of solvents to create the suspended bilayer and they are relatively fragile.

Early intervention for reading disabilities: teaching the alphabet principle in a connectionist framework.

Forty-eight children referred by teachers at the end of first grade for difficulty in reading were randomly assigned to three treatments, all of which modeled connections between written and spoken words but did not teach phonics rules, for eight half-hour individual tutoring sessions. The children were taught 48 words of varying orders of spelling-sound predictability (Venezky, 1995) using a whole-word method, for making connections between a word's name and its constituent letters; a subword method, for making connections between each color-coded spelling unit and its corresponding phonemes; or a combined whole-word and subword method. Regardless of the method used, children improved reliably on standardized reading measures and the taught words, showing that they could make connections between written and spoken words at the whole word and subword levels, even when rules were not taught. By posttest, the subword method showed a reliable advantage on a standardized test of real word reading. Knowledge of sounds associated with both multiletter and single-letter spelling units predicted reading achievement. Order of spelling-sound predictability (easy, moderate, difficult) was correlated with standardized measures of reading at pretest and posttest, and the magnitude of the relationship increased as a result of the intervention. Individual differences in verbal intelligence, rapid automatized naming, and phonological and orthographic skills predicted response to the intervention. Instructional implications of the results are discussed.

Novel ligands for the affinity labelling of luteinizing hormone releasing hormone receptors.

A number of novel luteinizing hormone releasing hormone (LHRH) analogues incorporating biotin together with potential covalent attachment sites have been synthesized. Those based on the des-Gly10-[D-Lys6]-LHRH ethylamide peptide backbone resulted in the most useful characteristics of binding to the LHRH receptor in rat anterior pituitary gland membranes. Of these, des-Gly10-[biotinyl-aminoethylglycyl-D-Lys6]-LHRH ethylamide (XBAL) gave the best specific: non-specific binding ratio, with 44 +/- 6% (+/- S.E.M.) of total binding being specific with a Kd of 131 +/- 16 pM (+/- S.E.M., n = 4) as determined by Scatchard analysis. Two methods have been used to covalently crosslink these analogues with the LHRH receptor; photoaffinity labelling and the use of homobifunctional N-hydroxysuccinimide ester crosslinkers. The photoaffinity analogues gave poor specific: non-specific binding ratios. Of the chemical crosslinkers tested, ethylene glycolbis(succinimidylsuccinate) (EGS) was found to be the most efficient at covalently linking the 125I-XBAL bound to the LHRH receptor site. At an EGS concentration of 5 mM, 23 +/- 3% (+/- S.E.M.) of the specific binding of 125I-XBAL was covalently crosslinked.

Facilitated calcium mobilization and inositol phosphate production in the priming effect of LH-releasing hormone in the rat.

The ability of LHRH to induce Ca2+ mobilization and production of inositol phosphates in rat anterior pituitary tissue in vitro was investigated in relation to the self-priming effect of LHRH. Prior exposure to LHRH (which caused a characteristic potentiation of subsequent secretory responses) specifically enhanced LHRH-induced inositol phosphate production and mobilization of intracellular Ca2+ stores. LHRH-induced influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels was unaltered, as was ligand binding to LHRH receptors. These data suggest that a novel facilitation of signalling may occur in the phospho-inositide-Ca2+ mobilization response mechanism during LHRH priming, and that this may represent an important means of regulating cellular responsiveness in gonadotrophs.

Solubilization of a large molecular weight form of the rat LHRH receptor.

The LHRH receptor has been solubilized from male rat anterior pituitary glands, using the zwitterionic detergent 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate in the presence of a high concentration of sodium chloride. This method gave high yields (up to greater than 70%) of the LHRH-binding site from the membrane preparation. Ligand binding studies using LHRH analogues were carried out to determine dissociation constants for LHRH receptors both in situ in the membrane preparation and for solubilized LHRH receptors. For all the analogues the binding characteristics were similar in both preparations, suggesting that the solubilization procedure left the LHRH receptor undenatured. Gel filtration revealed an apparent molecular weight for the LHRH receptor of 100,000-160,000, with the mean value being approximately twice that found by others using sodium dodecyl sulphate-polyacrylamide gel electrophoretic techniques. The results indicate that the LHRH receptor probably exists in gonadotroph membranes as a large complex of more than one subunit.