A 90-nm logic technology featuring strained-silicon

A leading-edge 90-nm technology with 1.2-nm physical gate oxide, 45-nm gate length, strained silicon, NiSi, seven layers of Cu interconnects, and low-/spl kappa/ CDO for high-performance dense logic is presented. Strained silicon is used to increase saturated n-type and p-type metal-oxide-semiconductor field-effect transistors (MOSFETs) drive currents by 10% and 25%, respectively. Using selective epitaxial Si/sub 1-x/Ge/sub x/ in the source and drain regions, longitudinal uniaxial compressive stress is introduced into the p-type MOSEFT to increase hole mobility by >50%. A tensile silicon nitride-capping layer is used to introduce tensile strain into the n-type MOSFET and enhance electron mobility by 20%. Unlike all past strained-Si work, the hole mobility enhancement in this paper is present at large vertical electric fields in nanoscale transistors making this strain technique useful for advanced logic technologies. Furthermore, using piezoresistance coefficients it is shown that significantly less strain (/spl sim/5 /spl times/) is needed for a given PMOS mobility enhancement when applied via longitudinal uniaxial compression versus in-plane biaxial tension using the conventional Si/sub 1-x/Ge/sub x/ substrate approach.     

Prolongation of the p53 response to DNA strand breaks in cells depleted of PARP by antisense RNA expression

The observation that 3-aminobenzamide, which inhibits a variety of ADP-ribose transferases, prolongs the gamma-irradiation-induced increase in intracellular p53 concentration suggested that one or more of such enzymes may determine the duration of the p53 response during G1 arrest. The role of poly(ADP-ribose) polymerase (PARP), an abundant nuclear enzyme activated by DNA strand breaks, in the p53 response to y-irradiation was investigated in Burkitt's lymphoma AG876 cells stably transfected with an inducible PARP antisense construct. Immunoblot analysis revealed that the cellular content of PARP was reduced to virtually undetectable levels after incubation of transfected cells for 72 h with the inducer dexamethasone. In noninduced antisense cells, the p53 concentration reached a maximum 2 h after exposure to 6.3 Gy of gamma-radiation and returned to control values by 4 h. In contrast, the p53 response in PARP-depleted antisense cells peaked at 4 h, with the levels of p53 remaining elevated for up to 12 h after y-irradiation. The maximal increase in p53 concentration was similar in both induced and noninduced cells. These results thus indicate that PARP activity, in part, determines the duration, but not the magnitude, of the p53 response to DNA damage.     

Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman's R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.     

Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting

The newly described uncoupling protein 3 (UCP3) may make an important contribution to thermogenesis in humans because of its high level of expression in skeletal muscle. Contrary to expectations, fasting, a condition that reduces resting energy expenditure, has been reported to increase UCP3 expression in muscle. We have confirmed that a 10-fold increase in UCP3 mRNA levels occurs in rat quadriceps muscle between 12 and 24 h of food removal. A less consistent twofold increase in muscle UCP2 mRNA levels was observed in animals fasted for up to 72 h. Administration of recombinant leptin to prevent a fall in circulating leptin levels did not eliminate the fasting-induced increase in quadriceps UCP3 expression. Administration of a high dose of glucocorticoid to fed animals to mimic the increase in corticosterone induced by fasting did not reproduce the increase in UCP3 expression observed in fasted animals. In contrast, elevation of circulating free fatty acid levels in fed animals by Intralipid plus heparin infusion caused significant increases in the UCP3/actin mRNA ratio compared with saline-infused fed controls in both extensor digitorum longus (2.01 +/- 0.34 vs. 0.68 +/- 0.11, P = 0.002) and soleus muscles (0.31 +/- 0.07 vs. 0.09 +/- 0.02, P = 0.014). We conclude that free fatty acids are a potential mediator of the increase in muscle UCP3 expression that occurs during fasting. This seemingly paradoxical induction of UCP3 may be linked to the use of free fatty acid as a fuel rather than an increased need of the organism to dissipate energy.     

O-GlcNAcylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization

BACKGROUND: Registered mortality from cryptogenic fibrosing alveolitis (CFA) in England and Wales has increased substantially since the specific International Classification of Diseases code for CFA was introduced in 1979. However, since a significant proportion of deaths from CFA are misclassified as post inflammatory fibrosis (PIF), it is possible that the observed rise in CFA mortality is due to diagnostic transfer from this code. To investigate this, and to assess mortality trends in other countries, annual CFA and PIF mortality data from England and Wales, USA, Australia, Scotland, Canada, New Zealand, and Germany were analysed. METHODS: Crude annual mortality rates were calculated and rates standardised by Poisson regression to allow assessment of changes over time and comparison between countries, sexes, and age groups. The relative trends in mortality from CFA and PIF were assessed by calculating the annual ratio of CFA to PIF deaths. RESULTS: Men were more likely than women to die from both CFA and PIF in all countries. The highest standardised CFA mortality rate occurred in England and Wales, and the lowest in Germany. Since 1979 mortality from CFA has increased in England and Wales, Australia, Scotland and Canada, but there was no trend in CFA mortality in New Zealand or Germany. In the USA mortality from CFA was low and has fallen. Mortality from PIF increased in all countries except New Zealand and Germany, and the highest PIF mortality, together with the greatest increase over time, was seen in the USA. Changes over time in the annual ratio of CFA to PIF deaths in all countries were small, implying that diagnostic transfer is not a major cause of the increasing CFA mortality. CONCLUSIONS: Mortality from CFA continues to increase in England and Wales and in many other countries. Diagnostic transfer from PIF does not appear to be a major cause of this.     

Effect of immunotherapy on sCD23 levels in patients allergic to Hymenoptera venom

BACKGROUND: sCD23 is the designation given to the low affinity IgE receptor. The soluble fragment of this receptor (sCD23) participates in the regulation of IgE synthesis. OBJECTIVE: The purpose of this study is to examine the effect of a venom immunotherapy regimen on sCD23 levels. METHODS: We measured sCD23 levels by ELISA in Hymenoptera venom-allergic patients (positive skin tests and a history of systemic reactions to Hymenoptera sting) in serial sera collected over a course of venom immunotherapy with a mean duration of 54 months. Mean pre-sCD23 and post-sCD23 levels were compared using a Student's two-tailed t test. RESULTS: sCD23 levels were found to be unchanged over the course of venom immunotherapy. CONCLUSIONS: This is the first longitudinal study that has been done. It suggests that while both immunotherapy and sCD23 are known to be involved in the regulations of IgE synthesis in the atopic patient, the immunomodulation seen in venom immunotherapy is not mediated through sCD23 in any simple regulatory manner.     

Lower caliceal stone clearance after shock wave lithotripsy or ureteroscopy: the impact of lower pole radiographic anatomy

PURPOSE: We determine whether there is a significant relationship between the spatial anatomy of the lower pole, as seen on preoperative excretory urography (IVP), and the outcome after shock wave lithotripsy or ureteroscopy for a solitary lower pole caliceal stone 15 mm. or less. MATERIALS AND METHODS: Between January 1992 and June 1996, 34 patients with 15 mm. or less solitary lower pole stone underwent ureteroscopy with intracorporeal lithotripsy (13) or extracorporeal shock wave lithotripsy (ESWL) with a Dornier HM3 lithotriptor (21). On pretreatment IVP lower pole infundibular length and width, infundibulopelvic angle of the stone bearing calix were measured. Stone size and area were determined from an abdominal plain x-ray. A plain x-ray of the kidneys, ureters and bladder was obtained in all patients at a median followup of 12.3 and 8 months in the ureteroscopy and ESWL groups, respectively. RESULTS: After initial therapy the overall stone-free rate was 62 and 52% in the ureteroscopy and ESWL groups, respectively. Stone-free status after ESWL was significantly related to each anatomical measurement. Infundibulopelvic angle 90 degrees or greater, and infundibular length less than 3 cm. and width greater than 5 mm. were each noted to correlate with an improved stone-free rate after ESWL. In contrast, the stone-free rate after ureteroscopy was not statistically significantly impacted by these anatomical features, although a clinical stone-free trend was identified relating to a favorable infundibular length and infundibulopelvic angle. The infundibulopelvic angle was 90 degrees or greater in 4 stone-free patients (12% overall), including 2 who underwent ureteroscopy and 2 who underwent ESWL. On the other hand, in 2 and 4 stone-free patients (18% overall) who underwent ureteroscopy and ESWL, respectively, favorable radiographic features consisted of a short, wide but acutely angulated infundibulum with the infundibulopelvic angle less than 90 degrees, and infundibular length less than 3 cm. and width 5 mm. or greater. In contrast, in 4 and 6 patients (29% overall) who underwent ureteroscopy and ESWL, respectively, all 3 radiographic features were unfavorable with the infundibulopelvic angle less than 90 degrees, and infundibular length greater than 3 cm. and width less than 5 mm. In these cases the stone-free rate was 50 and 17% after ureteroscopy and ESWL, respectively. CONCLUSIONS: The 3 major radiographic features of the lower pole calix (infundibulopelvic angle, and infundibular length and width) can be easily measured on standard IVP using a ruler and protractor. Each factor individually has a statistically significant influence on stone clearance after ESWL. A wide infundibulopelvic angle or short infundibular length and broad infundibular width regardless of infundibulopelvic angle are significant favorable factors for stone clearance following ESWL. Conversely, these factors have a cumulatively negative effect on the stone clearance rate after ESWL when they are all unfavorable. In ureteroscopy spatial anatomy has less of a role in regard to stone clearance but it may have a negative impact when there is uniformly unfavorable anatomy.     

Studies of the coronary circulation in Chagas' heart disease

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.     

Spectroscopic imaging of the knee with line scan CPMG sequences

OBJECTIVE: A line scan spectroscopic imaging method providing variable T2-weighted spectra from many small voxels along selected tissue columns was applied to study the chemical composition of hematopoietic and fatty marrow in the knees of adults and children. MATERIALS AND METHODS: Line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequences were implemented on a 1.5 T clinical scanner. Variable T2-weighted proton spectra from 128 locations along 20 cm long, 5 mm2 columns oriented superiorly to inferiorly through knees were collected from eight healthy adults and eight children. RESULTS: In adult yellow marrow, olefinic protons, water, a composite lipid proton peak, and methyl/methylene protons contributed 6.4 +/- 0.4, 4.2 +/- 1.5, 7.2 +/- 0.5, and 82.2 +/- 1.9% (mean +/- SD) to the spectra, respectively. Marrow spectra were largely independent of position along the column. Marrow spectra of normal children showed distinct positional dependences. Epiphyseal marrow spectra of children (8-16 years old) resembled adult spectra but with more water (mean 15 vs. 4%). Metaphyseal marrow had higher, variable water content, reflecting the extent of marrow conversion and generally obscuring the olefinic proton peak. CONCLUSIONS: Spectroscopic imaging of columns is a time-efficient method for sampling extensive regions of bone marrow with high spatial resolution. It should prove useful for proton spectroscopic studies of hematologic pathologies and conditions requiring the monitoring of lipid composition.