The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization, translation efficiency1,2, and has been proposed to provide a layer of “epitranscriptomic” gene regulation3. Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate “cap” in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD+) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria3–6. It has been proposed that NAD+, reduced NAD+ (NADH), and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps6–8. Here, we show instead that NAD+, NADH, and dpCoA are incorporated into RNA during transcription initiation, by serving as non-canonical initiating nucleotides (NCINs) for de novo transcription initiation by cellular RNA polymerase (RNAP). We further show that both bacterial RNAP and eukaryotic RNAP II incorporate NCIN caps, that promoter DNA sequences at and upstream of the transcription start site determine the efficiency of NCIN capping, that NCIN capping occurs in vivo, and that NCIN capping has functional consequences. We report crystal structures of transcription initiation complexes containing NCIN-capped RNA products. Our results define the mechanism and structural basis of NCIN capping, and suggest that NCIN-mediated “ab initio capping” may occur in all organisms

The thermodynamically most stable polymorph under ambient conditions is almost without exception the most desirable crystalline form for development by a pharmaceutical company. It is, therefore, beneficial to discover and to characterize this polymorph at the earliest possible stage of development. A screen for discovering the stable polymorph of a pharmaceutical compound early in the drug discovery-development process is developed and described. In this screen, a small amount of compound is suspended in a diverse group of solvents for two weeks in an effort to crystallize the most stable polymorph. The solubility of the compound in each solvent utilized in the stable polymorph screen is also simultaneously determined using a simple gravimetric method. Ritonavir and an early development candidate (Pfizer compound A) are used as model compounds to demonstrate the utility of the screen for finding the stable polymorph early in the drug discovery-development process.

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A new etchant for n and p bulk GaAs is described. Etching is accomplished through an electrochemical anodic process which uses NH4OH : H2O at a pH of 10.6–13.4. Etching rates depended on the current passed through the solution, while conductivity in turn depended on the pH of the solution. A large number of n+ GaAs polished wafers were characterized with this etching method. Samples etched showed growth-induced striations, dislocations, and twin lamellae. Etching was done on {111}-, {1̄1̄1̄}- {211}-, {511}-, and {110}- as well as {100}-oriented substrates with comparable results.

The fabrication and performance characteristics of an independently controllable closely spaced dual wavelength laser structure are described. The laser structure utilizes semi-insulating (Fe-doped InP) layers both for confinement of the current to the active regions and for separation of the active regions of the two lasers. Both lasers emit in single frequencies near 1.55 μm by virtue of frequency selective feedback provided by a second order grating. The light coupled into a single mode fiber from both lasers is about 5 dB smaller than that for optimum coupling arrangement of each laser. Dual wavelength laser structures of this type are useful for wavelength multiplexed optical transmission systems.