Dissecting cAMP binding domain A in the RIalpha subunit of cAMP-dependent protein kinase. Distinct subsites for recognition of cAMP and the catalytic subunit

The two gene-duplicated cAMP binding domains in the regulatory subunits of cAMP dependent protein kinase are each comprised of an A helix, an eight-stranded beta-barrel, and a B and C helix (1). The A domain is required for high affinity binding to C, while the B domain regulates access to the A domain. Using a combination of a yeast two-hybrid screen coupled with deletion analysis, cAMP binding domain A of RI was dissected into two structurally and functionally distinct subsites, one that binds cAMP and another that binds the C subunit. The minimum stable subdomain required for binding to C in the 1-3 micromolar range is composed of residues 94-169, while residues 236-244, mapped to the C helix of cAMP binding domain A, were defined as a second surface necessary for high affinity (5-10 nanomolar) binding to C. This portion of the C helix, due to its position directly between the two subsites, serves as a molecular switch for either a cAMP-bound conformation or a C-bound conformation and can thus modulate interactions of cAMP binding domain A with cAMP, with C, and with cAMP binding domain B.     

Experimental demonstration of step-like dispersion profiling inoptical fibre for soliton pulse generation and compression

Generation of 100 GHz trains of 500-700 fs pulses using dual-frequency beat conversion in a step-like dispersion profiled fibre is reported. The authors believe that this is the first time the generation and compression of soliton pulses using such a fibre has been demonstrated. The fabrication of such fibre assemblies does not require any special facilities and relies only on conventional optical fibre technology. They believe that the use of profiling the fibre dispersion by fibre segments instead of continuously dispersion-decreasing fibre is not only possible but preferable in many applications     

Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy

PURPOSE: To determine the frequency and nature of hepatic toxicity associated with fluorouracil (5-FU) plus levamisole adjuvant therapy. PATIENTS AND METHODS: All patients had resection of stage II or stage III colon cancer and were randomized to receive observation only, levamisole alone, or 5-FU plus levamisole. Serial liver function studies were documented in 1,025 patients who did not develop recurrence during the year of therapy. RESULTS: One hundred forty-nine (39.6%) of 376 patients treated with 5-FU plus levamisole showed laboratory abnormalities consistent with hepatic toxicity, compared with 16.3% of 251 patients treated with levamisole alone and 16.1% of 398 untreated controls. Most common was elevation of alkaline phosphatase, frequently accompanied by elevations of transaminase or serum bilirubin. Characteristically, these changes were mild, not associated with symptoms, and resolved when therapy was stopped. In some instances, they were associated with elevated carcinoembryonic antigen (CEA) tests or with fatty liver seen on computed tomographic (CT) scan or liver biopsy. CONCLUSION: Mild and reversible hepatotoxicity is a common consequence of 5-FU plus levamisole adjuvant therapy, but this is only rarely symptomatic. However, the oncologist should be alert to this phenomenon, since the associated laboratory and imaging findings may simulate those associated with hepatic metastasis.     

Oxidation protection for carbon fibre composites

Carbon fibre-reinforced ceramic matrix composites are promising candidate materials for high-temperature structural applications such as gas turbine blades. In oxidizing environments at temperatures above 400°C, however, carbon fibres are rapidly oxidized. There is, therefore, a need to coat the composite in order to protect it against oxidation. This review identifies the requirements of an effective oxidation protection system for carbon fibre-reinforced ceramics and summarizes the work which has been carried out towards this goal over the last 50 years. The most promising coatings are those composed of several ceramic layers designed to protect against erosion, spallation and corrosion, in addition to possessing a self-healing capability by the formation of glassy phases on exposure to oxygen.     

Design, implementation and evaluation of a high-speed integratedHamming neural classifier

This paper describes a fixed-weight Hamming binary neural classifier chip suitable for applications where high-speed operation is required. The circuit uses switched current-mode techniques throughout and achieves classification in one forward pass through the network. The chip was realized in 2.4-μm n-well CMOS technology and was designed to recognize the integers 0-9. It achieved a classification rate of 10 MHz without any observable tendency to misclassification or instability     

Rate of seasonal spread of respiratory syncytial virus in a pediatric hospital

The rate of nosocomial respiratory syncytial virus (RSV) infection was measured in a large pediatric hospital using an incidence density method. The at-risk days for nosocomial RSV were summed during a defined winter period in which there were 54 admissions with community-acquired RSV infection giving a rate of 2.9 cases per 1,000 at-risk days (95% confidence interval, 0.3-5.4 per 1,000).     

Heart failure after myocardial infarct in decompensated diabetes mellitus. Acute therapy with catecholamines--long-term therapy with ACE inhibitor-loop diuretic combination

In a 63-year-old woman with longstanding type I diabetes mellitus, CAD and chronic heart failure, a subacute myocardial infarction developed, together with decompensation of cardiac function and diabetes and concurrent pneumonia. Acute heart failure with acute renal failure on top of diabetic nephropathy, and interstitial pulmonary edema was initially treated with hemofiltration and catechol amines together with antibiotic and perfusor-regulated insulin therapy, and systemic heparinization. Subsequent chronic treatment with digitalis, acetyl salicylic acid, insulin and a combination of an ACE inhibitor and a loop diuretic resulted in an improvement of heart failure to NYHA functional class II where PTCA of coronary multi-vessel disease could be performed with low risk.