Two recently identified pro-inflammatory proteins, namely, neutrophil activating peptide 1 (NAP-1) [also termed interleukin-8 (IL-8)] and NAP-2, were chemically synthesized, purified, and characterized. The fully protected NAP-1/IL-8 (72 residues) and NAP-2 (70 residues) peptide chains were assembled by automated solid-phase methods with average stepwise yields of 99.5 and 99.3%, resulting in overall chain assembly yields of 70 and 62%, respectively. Deprotection resulted in crude products, which were allowed to fold by air oxidation, and were purified by two cycles of reverse-phase high-pressure liquid chromatography, yielding 27 mg of NAP-1/IL-8 and 22 mg of NAP-2. Purity was established by reverse-phase high-pressure liquid chromatography and isoelectric focusing, and the primary structures of the purified products were verified by using mass spectrometry and Edman sequencing methods. Synthetic and recombinant NAP-1/IL-8 were equally active on human neutrophil granulocytes as determined by measuring the induction of cytosolic free calcium, elastase release, and chemotaxis. Synthetic NAP-2 was equivalent to purified natural NAP-2 in the elastase release and calcium mobilization assays, but it was consistently less potent (3-5-fold) as a stimulus of chemotaxis, perhaps indicative of additional chemotactic components in the natural preparation. The results indicate that by chemical synthesis these cytokines can be obtained in purity and quantities suitable for further structural analysis, as well as functional studies both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Ion-spray mass spectrometry was investigated for the analysis of three marine neurotoxins: domoic acid, saxitoxin and tetrodotoxin. All three compounds gave positive-ion spectra with abundant ions of protonated molecules and no significant fragmentation. Domoic acid gave a negative-ion spectrum with a strong [M-H]- ion. Tandem mass spectrometry provided useful fragment-ion spectra for all compounds. Detection limits for flow injection analyses with selected-ion monitoring were determined to be 30 pg for saxitoxin, 100 pg for domoic acid and 200 pg for tetrodotoxin. Combining liquid chromatography with ion-spray mass spectrometry allowed the determination of domoic acid and some of its isomers in toxic shellfish tissue extracts.
A technique to detect local hot spots in thin aluminum film is discussed in this paper. Electromigration damaged aluminum films of different dimensions have higher effective noise temperatures than undamaged films (good conductors) when they have the same environmental temperature and carry the same current density. The differences in noise temperature are attributed to film local joule heating associated with voids or poor film adhesion to the substrate.
Shallow Trench Isolation (STI) has been the isolation scheme of choice for sub-0.25µm technologies.One of the challenges of scaling STI to 0.13µm and beyond is the control of Vt and Idsat of narrow devices. In this paper, we show that Idsat of narrow devices is strongly impacted by the stress due to trench processing. We also show that Vt and leakage of narrow devices (in particular NMOS devices) is impacted by dopant redistribution in the channel caused by TED (Transient Enhanced Diffusion) and boron segregation to the trench sidewalls.
Device FabricationNarrow devices developed for a 0.15µm technology were used for this study. In this process, a 2900A trench with an 80° slope is etched using an oxide-nitride-SiON hard mask. Bottom trench corners are rounded during the etch. A pad oxide undercut is used to promote the trench corner rounding followed by an RTO liner oxidation at 1150°C. The high temperature liner oxidation is used to minimize stress, achieve a greater than 50nm radius of curvature in the trench corners (Fig 1) and minimize silicon consumption (∆W<0.02µm) [1]. The trench is then filled by an HDP oxide followed by a high temperature N2 densification. An endpoint algorithm and high selectivity slurry are used to improve the CMP uniformity. The transistors use dual doped poly and a 30A nitrided oxide. Nitride spacers and cobalt salicide are used in this process.Transistors were oriented along the [110] direction, normal to the wafer flat. Fig 1-An RTO liner oxide is used to round the trench corners.
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