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New agents directed against molecular targets have now been tested in large prospectively randomized clinical trials for patients with untreated advanced non-small cell lung cancer (NSCLC). The trials have included small molecule inhibitors of receptor tyrosine kinases (gefitinib and erlontinib), monoclonal antibodies directed against either the ligands (bevicizumab against vascular endothelial growth factor) or their receptors (trastuzumab against ErbB2) and antisense nucleotides directed against mRNA coding for molecular targets (ISIS 3521 against protein kinase C alpha). The largest mature trials have included agents directed against ErbB1 (epidermal growth factor receptor). Two different small molecule inhibitors of erbB1 (gefitinib and erlontinib) and have been tested in 4 large international randomized trials. Two trials treated patients with advanced NSCLC with either gemcitabine and cisplatin or the same chemotherapy drugs combined with two different doses of gefitinib or one dose of erlontinib (INTACT 1 and TALENT). The other two trials treated patients with advanced NSCLC with either paclitaxel and carboplatin or the same chemotherapy drugs combined with either one of two doses of gefitinib or a single dose of erlontinib (INTACT 2 or TRIBUTE respectively). The results of INTACT 1 and INTACT2 showed no significant difference in survival between those treated with conventional combination chemotherapy and those treated with the same chemotherapy plus gefitinib. The results of the TRIBUTE and TALENT studies showed their primary endpoints of improving overall survival were not met. The monoclonal antibody, bevacizumab, is being tested in an ongoing clinical trial. The trial will compare the outcome of patients with untreated advanced adenocarcinoma of the lung treated with paclitaxel plus carboplatin to those treated with the same chemotherapy drugs plus bevacizumab. The results are scheduled to be available in 2005–2006. Although the initial trials adding newly developed molecular targeted agents have not shown initial success when added to conventional combination chemotherapy, further clinical trials are needed to ultimately define their role in the treatment of non-small cell lung cancer.

This paper presents and applies a methodology for determining the optimal scale, type, and timing of IC manufacturing capacity additions when demand is uncertain. Using the methodology, six different 200-mm fab designs are evaluated, including standard 10 K- and 20 K-wafer start per month (ws/mo) facilities, a 5 K-ws/mo "minifab," and "sequentially deployable" or "expandable" 10 K- and 20 K-ws/mo facilities. The results suggest that in the presence of uncertainty, manufacturers should follow a conservative deployment policy (better late than early to avoid periods of costly underutilization). In addition, when optimally deployed, larger, more efficient facilities are economically more viable than smaller fabs, since they are capable of generating substantially larger profits with comparable risks of loss, Sequentially deployable large fabs are even more attractive since they offer the economies of scale of larger fabs but require a smaller initial capital outlay.

The new Philips TL01 narrow-band (311-313 nm) and conventional broad-band (e.g., Philips TL12; 270-350 nm) sources are effective for psoriasis phototherapy, for which treatment regimens are based on a predetermined minimal erythema dose. TL01 phototherapy treatment times are approximately half those with TL12 for psoriasis, whereas the cumulative exposure doses at clearing are similar. We compared the phototumorigenic potential of TL01 and TL12 radiation in mouse skin. Groups of albino Skh-1 hairless mice were exposed for 5 d/week at three dose levels. At each dose level, TL12 and TL01 doses were equally edematogenic. At each dose level, TL01 radiation was significantly more effective at producing first tumors of 1 mm in diameter and multiple tumors. At the lower two dose levels, TL01 radiation produced a significantly greater proportion of squamous cell carcinomas. This study demonstrates that TL01 radiation is more phototumorigenic than TL12 radiation at equally edematogenically weighted doses. This is in contrast with previous reports that edema production by polychromatic sources is predictive of their phototumorigenic effect in Skh-1 mice. The absolute cumulative TL12 dose needed to induce tumors was much less than that for TL01 radiation. The possibility of increased tumor risk with TL01 phototherapy should be considered but must be balanced against the high phototherapeutic efficacy of this source, short treatment times, and the low cumulative doses necessary for clearing of psoriasis.

Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.

The stability of polysilicon sheet resistance was studied as a function of conventional furnace anneal (CFA) and rapid thermal anneal (RTA). Polysilicon films of 100, 200, and 300 nm thickness were doped with boron, borofluoride, arsenic, or phosphorus and subjected to a CFA anneal matrix simulating the thermal cycles of a digital base BiCMOS process. RTA was introduced at the beginning or the end of the CFA anneal cycle to study its effectiveness in stabilizing the sheet resistance. CFA temperature was varied from 550 to 900 degrees C, and RTA temperature from 900 to 1100 degrees C. Throughout this range, it was found that the resistance depends primarily on the final anneal temperature and duration. The resistance increases substantially when the samples are subjected to a final low temperature anneal cycle, and decreases dramatically when followed by high temperature RTA. This was observed for arsenic- phosphorus-, and boron-doped films. It is suggested that the duration of cooling plays an important role in determining the nominal film resistance, thus explaining the efficiency of RTA in reducing and stabilizing the resistance. The results are compared with available models on dopant redistribution and carrier transport in polysilicon films. >

The question of which C ∗ -algebras have only inner derivations has been considered by a number of authors for 25 years. The separable case is completely solved, so this paper deals only with the non-separable case. In particular, we show that the C ∗ -tensor product of a von Neumann algebra and an abelian C ∗ -algebra has only inner derivations. Other special types of C ∗ -algebras are shown to have only inner derivations as well such as the C ∗ -tensor product of L ( H ) (all bounded operators on separable Hilbert space) and any separable C ∗ -algebra having only inner derivations. Derivations from a smaller C ∗ -algebra into a larger one are also considered, and this concept is generalized to include derivations between C ∗ -algebras connected by a ∗ -homomorphism. Finally, we consider the general problem of a sequence of linear functionals on a C ∗ -algebra which converges to zero (in norm) when restricted to any abelian C ∗ -subalgebra. Does such a sequence converge to zero in norm? The answer is “yes” for normal functionals on L ( H ), but unknown in general.

Let U be a von Neumann algebra acting on a Hilbert space H. If T is the sum of an element of U′ and a compact operator, then TA-AT is compact for all U′. The basic problem considered in this paper is whether the converse statement holds. The converse is shown to be true if U does not contain certain Type II1 factors as direct summands. No examples are known for which the converse fails. Examples are given indicating the extent to which the main result holds when U is abelian and not weakly closed. The main result leads to a number of theorems on representations of derivations and automorphisms of the algebra of operators on H generated by U and the compact operators.

Summary Four commercially available, medium pressure mercury sun lamps were used to assess their effects on promoting vitamin D synthesis in the skin. It was found that all the lamps studied had vitamin D synthesizing spectral wavelengths and caused an increase in the serum concentrations of 25-hydroxyvitamin D. However, the ultraviolet and visible irradiance measurements showed that a considerable proportion of the ultraviolet radiation was below 290 nm. It was not surprising, therefore, to find that these lamps caused adverse skin reactions. While a useful rise in vitamin D production can be obtained with these sun lamps, the difficulty involved in avoiding skin reaction limits their usefulness. Such lamps are unlikely to provide a safe practical routine method for the prevention of vitamin D deficiency in the home.