Introduction. Glycine is one of the major inhibitory neurotransmitters in the spinal cord and brain stem of vertebrates. 1 The inhibitory actions of glycine are mediated by the strychnine-sensitive glycine receptor (ssGlyR), a ligand-gated chloride channel distributed throughout the spinal cord and brain stem. 2 Glycine is also known to potentate the action of glutamate acting as an essential co-agonist on postsynaptic N-methyl-D-aspartate (NMDA) receptors. 3 Synaptic levels of glycine are believed to be controlled by high-affinity glycine transporters. These transporters are members of a large family of sodium/chloride-dependent transporters, which are composed of single oligomeric proteins containing 12 hydrophobic membrane-spanning domains. 4 Molec-

Glecaprevir was identified as a potent HCV NS3/4A protease inhibitor, and an enabling synthesis was required to support the preclinical evaluation and subsequent Phase I clinical trials. The enabling route to glecaprevir was established through further development of the medicinal chemistry route. The key steps in the synthesis involved a ring-closing metathesis (RCM) reaction to form the 18-membered macrocycle and a challenging fluorination step to form a key amino acid. The enabling route was successfully used to produce 41 kg of glecaprevir, sufficient to support the preclinical evaluation and early clinical development.

[reaction: see text] Treatment of a variety of alcohols, amines, and N-hydroxylamines with 2,2,2-trifluoroethyl formate gave the corresponding formylated adducts in high yields.

Neurotransmitter transport systems are major targets for therapeutic alterations in synaptic function. We have cloned and sequenced a cDNA encoding the human type 2 glycine transporter GlyT2 from human brain and spinal cord. An open reading frame of 2391 nucleotides encodes a 797 amino acid protein that transports glycine in a Na + /Cl^-dependent manner. When stably expressed in CHO cells, human GlyT2 displays a dose-dependent uptake of glycine with an apparent K m of 108 W WM. This uptake is not affected by sarcosine at concentrations up to 1 mM. Radiation hybrid analysis mapped the GlyT2 gene to D11S1308 (LOD = 8.988) on human chromosome 11p15.1^15.2.z 1998 Federation of European Biochemical Societies.

Alternate assessments have been used for the last 10 years to evaluate schools' efforts to teach children with significant cognitive disabilities. However, few studies have examined the reading skills of children who participate in these assessments. The purpose of this study was to extend understanding of the reading skills of this population by administering early-grade word and passage reading fluency curriculum-based measures to a sample of 7,440 students in Grades 3 through 8 and 11. Overall, the performance on curriculum-based measures and the relationship with alternate assessment performance varied based upon disability, grade, and level of alternate assessment. The authors discuss implications for test developers and teachers along with future directions for research.

The solution phase synthesis of a 167-member library of isocoumarins is described. The key intermediates for library generation, 4-iodoisocoumarins, are easily prepared by iodocyclization of the corresponding 2-(1-alkynyl)arenecarboxylate esters. The 4-iodoisocoumarins undergo palladium-catalyzed Sonogashira, Suzuki-Miyura and Heck reactions to yield a diverse set of isocoumarins. Alternatively, isocoumarins, bearing hydroxyl or bromine functionalities, have been prepared by ZnCl2 and Pd(PPh3)4 mediated cyclization of the corresponding o-iodobenzoic acid and appropriate terminal alkynes. The resulting isocoumarins were further diversified by derivatization of the hydroxyl or bromine groups. A small set of isoquinolinones were also prepared from the corresponding isocoumarins.

In this review, we explore the extent to which researchers evaluating the efficacy of Tier 2 elementary reading interventions within the framework of Response to Intervention reported on fidelity of implementation and alignment of instruction between tiers. A literature search identified 22 empirical studies from which conclusions were drawn. Results suggest that fidelity of implementation is typically monitored at Tier 2 and that alignment between tiers of intervention is often apparent yet not explicitly stated. However, researchers frequently neglect to report on fidelity of intervention in Tier 1, potentially limiting claims that can be made about the efficacy of subsequent Tier 2 intervention. Limitations and implications for future research are discussed.

Improved procedures are described for the synthesis of meso~tetra• kis(2,6-dichlorophcnyl)porphyrin and for subsequent perhalogcnation of the porphyrin ring.