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Highlights: [•] LaLuO3 and LaScO3 layers were treated by flash lamp annealing. [•] FLA does not affect the very low leakage currents or the k-values of and LaScO3. [•] TiN oxidation in a gate-first processing scheme can be prevented by a Si-cap on TiN. [•] MOS capacitors are evaluated for oxide charges. [Copyright &y& Elsevier]

Switch costs in task switching are often assumed to reflect the strengthening of task-related associations. Recently, we provided evidence that committing an error leads to the strengthening of the wrong task (Steinhauser & Hübner, 2006). In the present study, we report how error-induced control compensates for the effects of error strengthening. We hypothesized that, although error detection cannot prevent an error from being strengthened, it initiates processes that suppress the negative consequences of error strengthening on subsequent trials. Because error-induced control is known to operate slowly, we predicted that a compensatory effect should be observable only for slow responses. In three task-switching experiments, these predictions were confirmed by distributional analyses. The results extend our understanding of the interplay between procedural learning and executive control. [ABSTRACT FROM AUTHOR]

We investigated the hypothesis that mixing costs intask shifting reflect th e sequential selection of task components (e.g., stimulus categories) during task execution. This proposition was supported by Hübner, Futterer, and Steinhauser (2001), who showed that the amount of mixing costsdepends on the number of mixed task components (e.g., stimulus level and judgment). However, their results could also be explained by a task set selection account, because task components and task sets were confounded. In Experiments 1 and 2, we compared conditions in which either the number of task sets varied and the number of mixed task components was constant or vice versa. Only the number of mixed task components was predictive for the mixing costs. In Experiment 3, we replicated the additivity of mixing costs from level a ndjudgment mixing. Our results suggest thatthe mixingcosts reflect a selection strategy in which interference is reduced in a stepwise manner. [ABSTRACT FROM AUTHOR]

Structural changes at annealing temperatures (Tan) of 500–1,100°C were investigated for thin Ta films which were sputter-deposited onto pure Si substrates and onto thermally oxidized Si. In the as-deposited state, the Ta layers predominantly consist of metastable tetragonal β-Ta, whereby the [001] texture is independent of the substrate material. At lower annealing temperatures, the microstructural evolution is essentially the same for both Ta films. Incorporation of O atoms causes an increase of the intrinsic compressive stress, and diffusion of C atoms into the Ta layer leads to the formation of Ta2C. Additionally, a partial transformation of the original β-Ta phase into a second phase with tetragonal unit cell (denoted as β′-Ta) occurs. For the Ta/Si system, the formation of a Ta–Si intermixing layer is initiated at Tan=550°C, and nucleation of crystalline TaSi2 occurs at Tan=620°C. The formation of a second Ta silicide was not detected up to Tan=900°C. In the case of the Ta film deposited onto the SiO2 substrate, the metastable β-Ta and the β′-Ta transform completely into the thermodynamically stable cubic α-Ta at Tan=750°C. A marked reaction with the substrate indicated by the formation of Ta2O5 and Ta5Si3 occurs at Tan=1,000°C. [ABSTRACT FROM AUTHOR]

The tolerability and safety of candesartan cilexetil has been evaluated in over 5000 subjects enrolled into double-blind or open-label clinical studies. In double-blind clinical trials in patients with primary hypertension, candesartan cilexetil 2-16 mg once-daily was associated with a low incidence of adverse events and drug-related withdrawals, similar to placebo. The drug showed no evidence of dose-dependent adverse events and it was equally well tolerated by men and women and by elderly (⩾65 years) and younger (<65 years) patients alike. Candesartan cilexetil had no effect on blood glucose control or serum lipid profile in patients with type II diabetes. It was very well tolerated also when given in combination with hydrochlorothiazide or amlodipine and during long-term open-label therapy (up to 1 year). Candesartan cilexetil therefore possesses an excellent tolerability profile that extends to a wide variety of patients including the elderly and it does not aggravate co-existing risk factors such as hyperlipidaemia or glucose intolerance. It therefore appears to offer a better tolerated alternative to other commonly used antihypertensive agents. [ABSTRACT FROM AUTHOR]

Candesartan cilexetil is rapidly and completely hydrolysed to the active compound candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, long-acting, selective angiotensin II AT1 receptor blocker. The pharmacokinetics of candesartan were investigated after single and repeated once-daily doses of candesartan cilexetil in the dose range 2-16 mg in both younger (19-40 years) and elderly (65-78 years) healthy volunteers in five studies. Blood pressure, heart rate, and hormones associated with the renin-angiotensin system, and safety of candesartan cilexetil administration were also assessed. Placebo comparisons were made in four studies. Frequent blood samples were collected after the first single dose of candesartan cilexetil, and during the last dosing interval after 1 week repeated once-daily administration. Serum and plasma were analysed for candesartan cilexetil, candesartan and its inactive metabolite, CV-15959, as well as angiotensin I and II, aldosterone, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity. The AUC and Cmax of candesartan showed dose-proportional increases in the dose range of 2-16 mg candesartan cilexetil after both single and repeated once-daily tablet intake, indicating linear pharmacokinetics in both younger and elderly healthy subjects. The pharmacokinetics did not change on repeated dosing and, as expected from the half-life of candesartan of approximately 9 h in younger subjects, there was almost no accumulation after repeated once-daily dosing. The time to peak candesartan concentrations after tablet intake was consistently approximately 4 h at all dose levels. Both Cmax and AUC of candesartan were increased after single and repeated once-daily dosing in the elderly compared to younger subjects by approximately 50%. However, no accumulation after repeated once-daily dosing were seen in the elderly. The half-life of candesartan in the elderly (9-12 h) was somewhat longer than in the younger healthy adult volunteers (approximately 9 h) and no gender-related differences in the disposition of candesartan were observed. Serum concentrations of CV-15959 were much lower than candesartan, and reached peak serum concentrations later, about 4-9 h after dose intake. The elimination of CV-15959 was somewhat slower than that of candesartan. Candesartan cilexetil, the prodrug to candesartan, was not measurable in serum. No differences in ACE activity or serum aldosterone concentrations were observed between subjects receiving candesartan cilexetil and placebo tablets. Plasma angiotensin I and II concentrations and PRA were augmented after single doses and further increased after 1 week repeated candesartan cilexetil dosing. Single and repeated doses of candesartan cilexetil were well tolerated in the younger and elderly volunteers. Only mild adverse events were recorded, with `headache' as the most commonly reported event, and no increase in the number of reported adverse events was observed with higher doses of candesartan cilexetil. No clinically significant changes in respect to vital signs, physical examination, ECG, and clinical laboratory tests were observed. [ABSTRACT FROM AUTHOR]

Candesartan is a new generation angiotensin II type 1 receptor blocker, characterised by tight binding to and slow dissociation from the receptor. In order to delineate the dose-response curve for candesartan cilexetil (the orally administered prodrug), results from six European placebo-controlled, dose-response studies were pooled. These were of a double-blind, randomised, parallel group design, with a treatment duration of 4-12 weeks. A total of 1482 patients with mild to moderate primary hypertension were treated with candesartan cilexetil 2 mg (n = 80), 4 mg (n = 216), 8 mg (n = 455) or 16 mg (n = 294), or with placebo (n = 437). Blood pressure (BP) measurements were performed 24 h after dose. The differences in BP change (baseline vs end of the studies) between the placebo group and the groups treated with candesartan cilexetil were assessed using analysis of covariance and dose response curves were estimated by fitting the data to an Emax model. The placebo-corrected mean reductions in sitting diastolic BP were approximately 2.5 mm Hg with 2 mg, 4.5 mm Hg with 4 mg, 6 mm Hg with 8 mg, and 8 mm Hg with 16 mg of candesartan cilexetil. For sitting systolic BP, the placebo-corrected mean reductions were in the order of 5, 7, 10 and 12 mm Hg, respectively, with 2, 4, 8 and 16 mg of candesartan cilexetil. The BP reductions were similar in the standing position with no indication of postural hypotension. Age or gender did not influence the BP response to candesartan cilexetil. In conclusion, candesartan cilexetil provides a clinically significant, dose-dependent antihypertensive effect in doses ranging from 4-16 mg once daily. [ABSTRACT FROM AUTHOR]

Background: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.Methods: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.Results: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.Conclusions: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers. [ABSTRACT FROM AUTHOR]