Validity of the thin mask approximation in extreme ultraviolet mask roughness simulations.

In the case of extreme ultraviolet (EUV) lithography, modeling has shown that reflector phase roughness on the lithographic mask is a significant concern due to the image plane speckle it causes and the resulting line-edge roughness on imaged features. Modeling results have recently been used to determine the requirements for future production worthy masks yielding the extremely stringent specification of 50 pm rms roughness. Owing to the scale of the problem in terms of memory requirements, past modeling results have been based on the thin mask approximation in this application. EUV masks, however, are inherently three-dimensional (3D) in nature and thus the question arises as to the validity of the thin mask approximation. Here, we directly compare the image plane speckle calculation results using the fast two-dimensional thin mask model to rigorous finite-difference time-domain results and find the two methods to agree to within 10% in the computation of the speckle magnitude and 20% in the computation of the line-edge roughness limited depth of focus. For both types of computation, the two-dimensional method provides a conservative estimate. The 3D modeling is also used to show that layer-to-layer correlated roughness is indeed the roughness metric of most concern.

Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction.

To define the mechanisms by which hPrP90-231 induces cell death, we analyzed its interaction with living cells and monitored its intracellular fate. Treatment of SH-SY5Y cells with fluorescein-5-isothiocyanate (FITC)-conjugated hPrP90-231 caused the accumulation of cytosolic aggregates of the prion protein fragment that increased in number and size in a time-dependent manner. The formation of large intracellular hPrP90-231 aggregates correlated with the activation of apoptosis. hPrP90-231 aggregates occurred within lysotracker-positive vesicles and induced the formation of activated cathepsin D (CD), indicating that hPrP90-231 is partitioned into the endosomal-lysosomal system structures, activating the proteolytic machinery. Remarkably, the inhibition of CD activity significantly reduced hPrP-90-231-dependent apoptosis. Internalized hPrP90-231 forms detergent-insoluble and SDS-stable aggregates, displaying partial resistance to proteolysis. By confocal microscopy analysis of lucifer yellow (LY) intracellular partition, we show that hPrP90-231 accumulation induces lysosome destabilization and loss of lysosomal membrane impermeability. In fact, although control cells evidenced a vesicular pattern of LY fluorescence (index of healthy lysosomes), hPrP90-231-treated cells showed diffuse cytosolic fluorescence, indicating LY diffusion through damaged lysosomes. In conclusion, these data indicate that exogenously added hPrP90-231 forms intralysosomal deposits having features of insoluble, protease-resistant aggregates and could trigger a lysosome-mediated apoptosis by inducing lysosome membrane permeabilization, followed by the release of hydrolytic enzymes.

Knowledge and attitudes of breast self examination in a group of women in Shiraz, southern Iran.

BACKGROUND: Breast cancer is the most common cause of cancer related deaths among women worldwide. The disease in women occurs at a younger age in Iran than in western communities. OBJECTIVE: To determine the practice of breast self examination (BSE) among 25-54-year-old women in Shiraz, southern Iran. METHODS: Using a stratified convenient sampling method, a total of 300 women aged 25-54 years who attended our health care centre between September 2006 and May 2007 were invited for an interview on BSE. All invited women accepted and were interviewed. The questions included demographic information, level of education, whether the participant performed BSE and, if yes, how and when. They were also asked about their source of information. RESULTS: The median (interquartile range (IQR)) age of participants was 38.5 (14) years. Of the 300 studied women, 283 (94.3%) were married; 160 (53.3%) performed BSE-9 (5.6%) of whom did BSE using a correct method and at an appropriate time. Of 140 non-performers, 74 (52.9%) did not know how to do BSE; the remaining women did not do BSE for fear of being found positive for cancer or did not care about it. Those who performed BSE learned it from medical personnel (n = 72, 49.4%), their relatives, and TV, radio, books, journals and pamphlets. Of those who performed BSE, 9 (5.6%) found an abnormal examination; 6 (3.8%) were found positive after further evaluation. The likelihood of performing BSE was not associated with educational level, marital status, age of participant, or how the participant learned about BSE. CONCLUSIONS: Considering that 46.7% of participants did not perform BSE, and that almost all of those who did perform BSE did it incorrectly-and taking into account that a lack of knowledge on how to perform BSE was the main reason why most non-performers did not examine themselves-establishing educational programmes to teach women at risk may help in the early diagnosis of breast cancer.

Interleukin-1 and inflammatory neurodegeneration.

Inflammation occurs rapidly in response to acute brain insults such as stroke, haemorrhage or trauma, and can be sustained for long periods of time, for example in Alzheimer's or Parkinson's diseases and multiple sclerosis. Experimental evidence indicates that inflammation plays a major role in neurodegeneration under these conditions, and that the cytokine IL-1 (interleukin-1) is a pivotal mediator. IL-1 is expressed rapidly in response to neuronal injury, predominantly by microglia, and elevated levels of endogenous or exogenous IL-1 markedly exacerbate injury. The naturally occurring IL-1RA (IL-1 receptor antagonist) markedly inhibits ischaemic, excitotoxic and traumatic brain injury in rodents, and has shown promise in a Phase II clinical trial in stroke patients. The mechanisms of IL-1 expression, release and action in neurodegeneration are not fully elucidated and appear multiple. Systemic IL-1 markedly enhances ischaemic brain injury via release of neutrophils into circulation, neutrophil adhesion to injured cerebrovasculature and CNS (central nervous system) invasion, and cell death via activation of matrix metalloproteinase-9. IL-1 also influences the release of toxins from glial and endothelial cells. Neuronal responses to excitotoxins and physiological factors may have an impact on neuronal survival. IL-1RA, delivered peripherally, can enter the CNS in animals and humans and has no adverse effects in stroke or subarachnoid haemorrhage patients, but shows potential benefit in acute stroke patients.

Comparative extreme ultraviolet emission measurements for lithium and tin laser plasmas.

Detailed spectroscopic studies on extreme UV emission from laser plasmas using tin and lithium planar solid targets were completed. At 13.5 nm, the best conversion efficiency (CE) for lithium was found to be 2.2% at intensities near 7 x 10(10) W/cm(2). The highest CE measured for tin was near 5.0% at an intensity close to 1 x 10(11) W/cm(2).

13.5 nm EUV generation from tin-doped droplets using a fiber laser.

A comprehensive study of the spectral and Mo-Si mirror inband EUV emission from tin-doped droplet laser plasma targets irradiated with a single 1064 nm beam from an Yb:doped fiber laser is reported.With pre-pulse enhancement, in-band conversion efficiency of approximately 2.1% is measured for laser irradiance intensities near 8 x 10(10) W/cm(2). This is the first study to be reported that uses a high-power, high repetition rate fiber laser with the high repetition rate droplet targets where EUV generation from plasmas is measured.

Neuroprotective agent chlomethiazole attenuates c-fos, c-jun, and AP-1 activation through inhibition of p38 MAP kinase.

Recent evidence suggests that stress-activated protein kinases expressed in glial cells have very important roles during cerebral ischemia. The neuroprotective agent chlomethiazole, which is known to enhance the conductance at the GABA(A) receptor complex, is presently in clinical trials for the treatment of severe stroke. Here the authors suggested that chlormethiazole has anti-inflammatory properties because it potently and selectively inhibited p38 mitogen-activated protein (MAP) kinase in primary cortical glial cultures. The inhibition of p38 MAP kinase resulted in the attenuation of the induction of c-fos and c-jun mRNA and AP-1 DNA binding by lipopolysaccharide (LPS). In addition, chlomethiazole inhibited the activation of an AP-1-dependent luciferase reporter plasmid in SK-N-MC human neuroblastoma cells in response to glutamate. Chlomethiazole inhibited the p38 MAP kinase activity as revealed by the decrease in the LPS-induced phosphorylation of the substrates ATF-2 and hsp27, whereas the phosphorylation status of the p38 MAP kinase itself was unaffected. Interestingly, chlomethiazole exhibited an IC(50) of approximately 2 micromol/L for inhibition of c-fos mRNA expression, indicating 25 to 75 times higher potency than reported EC(50) values for enhancing GABA(A) chloride currents. The results indicated a novel mechanism of action of chlomethiazole, and provided support for a distinctive role of p38 MAP kinase in cerebral ischemia.

Contribution of MAP kinase pathways to the activation of ATF-2 in human neuroblastoma cells.

Activated Transcription Factor-2 (ATF-2) is important during development of and during injury to the brain. Both Jun N-terminal Kinases (JNKs) and p38 Mitogen-Activated Protein Kinases (p38MAPKs) may phosphorylate ATF-2, but the contribution of these two pathways in cells has never been investigated. We have assayed endogenous p38MAPK activity in SK-N-MC and SH-SY5Y human neuroblastoma cells for activation of a GAL4/ATF-2 fusionprotein, by means of titrations of transfected expression plasmids and by using the p38MAPK inhibitor SB203580. It was found that basal activation of ATF-2 was independent of p38MAPK and that whereas MAPK kinase-3 (MKK3) was a weak inducer of ATF-2 activation, it was a potent activator of the stress activated transcription factor CHOP. In contrast, ATF-2 was very potently activated by the JNK pathway activator MAPK kinase kinase-1 (MEKK1). Thus, kinases downstream of MEKK1 appear relevant, but it is unlikely that p38MAPKs contribute quantitatively to activation of ATF-2 in these cells.

Post-translational inhibition of cytochrome P-450 2E1 expression by chlomethiazole in Fao hepatoma cells.

Chlomethiazole (CMZ) is a sedative and anticonvulsant drug that has been shown to be an efficient transcriptional inhibitor of expression of rat hepatic ethanol-inducible cytochrome P-450 2E1 (CYP2E1). Recent results have shown that human CYP2E1 expression in vivo is almost completely inhibited in control subjects and in alcoholic patients treated with CMZ. In the present investigation, we evaluated the mode of action of CMZ on CYP2E1 expression in Fao rat hepatoma cells. Transcriptional activity of the CYP2E1 gene was monitored using reverse transcription-polymerase chain reaction-based quantification of CYP2E1 heterologous nuclear RNA (hnRNA) against a mimic DNA standard, mRNA was detected by Northern blotting, enzyme protein was detected by Western blotting, and CYP2E1-dependent catalytic activity was detected by assay of chlorzoxazone-6-hydroxylation. Six hours after CMZ treatment, the levels of both CYP2E1 protein and catalytic activity were concomitantly reduced at an IC50 value of about 5 microM. Ethanol treatment of the cells caused a 2-fold induction of CYP2E1 protein levels, which was inhibited by CMZ. Change of medium unexpectedly caused an increase in CYP2E1 gene transcription 4 h later, as monitored by quantitative determination of CYP2E1 hnRNA. However, CMZ failed to influence the expression of CYP2E1 hnRNA or mRNA both constitutively and after medium change, indicating no effect on gene transcription or mRNA synthesis/stability. Cycloheximide treatment of the cells did not abolish the inhibitory action of CMZ, further indicating an action at the post-translational level; in addition, CMZ inhibited CYP2E1 expression in V79 cells with stably expressed CYP2E1 under the control of the SV40 promoter. The data indicate that the CYP2E1 gene is transcriptionally activated in response to medium change and that CMZ, apart from a transcriptional inhibitor of CYP2E1 expression, acts in addition as an efficient high-affinity post-translational inhibitor of CYP2E1, probably due to an allosteric destabilization of the enzyme. This indicates a very rapid and effective CMZ-mediated inhibition of CYP2E1 in vivo.

Further observations on the measurement of fatty acid incorporation by erythrocyte ghosts to quantify unbound palmitate concentration in albumin-palmitate mixtures.

Advantage has been taken of the extensive and reversible incorporation of long-chain fatty acids by erythrocyte ghosts to characterize the interaction of tritium-labeled palmitic acid with human serum albumin (pH 7.4, 37 degrees C). A stoichiometric binding constant for 1:1 complex formation (K1) of 4.6 (+/-0.3) x 10(8) M-1 was obtained from experiments in which erythrocyte ghosts were the source of fatty acid. An essentially identical estimate of 4.1 (+/-0.7) x 10(8) M-1 was obtained from a second series of experiments in which the [3H]palmitate was included with the albumin in the aqueous phase. The magnitude of the present K1 estimate, which is three- to fivefold larger than most recently reported values, reflects binding measurements restricted to a very limited range of unbound palmitate concentration (-0.2 nM) to ensure that the ligand is essentially monomeric. This use of erythrocyte ghosts to quantify the palmitate-albumin interaction has reinforced the basic tenets of a published procedure [I. N. Bojesen, and E. Bojesen (1992) J. Lipid Res. 33, 1327-1334], the major virtue of which is its ability to provide a direct measure of the equilibrium concentration of unbound fatty acid in albumin-palmitate mixtures.

[Occlusion of the upper mesenteric artery. Angiographic study and surgical treatment of 8 cases]. / Oclusão da artéria mesentérica superior. Estudo angiográfico e tratamento cirúrgico de 8 casos.

Eight patiants suffering from abdominal angina due to chronic intestinal ischemia have been submitted to angiographic examination and revascularization of superior mesenteric artery (SMA). All had the classical symptoms of postprandial pain, weight loss and abnormalities of the stools. The surgical procedure of choice was bypass from abdominal aorta to SMA. The reimplantion of SMA was performed in 2 cases. The results was good in 87,5% of cases. The mortality in acute intestinal ischemia is high, and 50% of such patients have previous attacks of abdominal angina. If the diagnosis is established by engiography, the revascularization should be performed.