Introducing the Intel i860 64-bit microprocessor

The authors describe the single-chip i860 CPU, a 64-bit, RISC (reduced-instruction-set-computer)-based microprocessor that executes parallel instructions using mainframe and supercomputer architectural concepts. They designed the 1,000,000-transistor, 10-mm×15-mm processor for balanced integer, floating-point, and graphics performance. They discuss the RISC core, memory management, floating-point unit, graphics, bus interface, software support, and interfacing to a DRAM system     

Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase

Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole).     

AHP-Based Equipment Selection Model for Construction Projects

Selection of equipment for construction projects, a key factor in the success of the project, is a complex process. Current models offered by the literature fail to provide adequate solutions for two major issues: the systematic evaluation of soft factors, and the weighting of soft benefits in comparison with costs. This paper presents a selection model based on analytic hierarchy process (AHP), a multiattribute decision analysis method, with a view to providing solutions for these two issues. The model has the capacity to handle a great number of different criteria in a way that truly reflects the complex reality, to incorporate the context and unique conditions of the project, and to allow for manifestation of user experience and subjective perception. The model was implemented in an in-house developed system that was improved and validated through testing by senior professionals. The main academic contribution of the study is in the modification of AHP to correspond with the nature of equipment selection and in its utilization as an effective means for the formalization of knowledge possessed by competent, experienced practitioners. On the practical side, the proposed model offers an efficient, convenient tool that forces the users into orderly, methodical thinking, guides them in making logical, consistent decisions, and provides a facility for all necessary computations.     

A new clinical classification for hospital prognosis of unstable angina pectoris

Unstable angina represents a heterogeneous spectrum of clinical entities between chronic stable angina and acute myocardial infarction. To facilitate prognostication of in-hospital outcome, we prospectively tested on a priori unstable angina classification scheme based on information available at the time of acute presentation. Prospective database enrollment at the time of emergency room presentation was performed and patients were classified into 1 of the following categories: class IA, acceleration of previous exertional angina without electrocardiographic (ECG) changes; class IB, acceleration of previous exertional angina with ECG changes; class II, new-onset exertional angina; class III, new-onset rest angina; class IV, protracted rest angina with ECG changes. The study consisted of 1,387 consecutive patients with unstable angina. Baseline demographics and aggregate in-hospital major cardiac event rates were recorded (myocardial infarction, refractory angina, and death). There was a significant increasing trend in cardiac events from class I to IV (p < 0.0001). Class IA patients had the lowest aggregate event rate at 2.7% (p = 0.0005). Paired chi-square tests of adjacent categories showed no differences in event rates for class IB and II (p = 0.3). A significantly higher rate of adverse events was seen for class III patients (20.1%, p < 0.0001). Class IV patients demonstrated the highest rate of in-hospital adverse events (42.8%, p < 0.0001). We conclude that this easily deduced, universally applicable categorization of unstable angina is highly prognostic of in-hospital adverse cardiac events and hence could have potential use for triage decisions regarding hospital admission and intensity of therapy.     

Identification of effector binding sites on S100 beta: studies with guanylate cyclase and p80, a retinal phosphoprotein

S100 beta is a calcium-binding protein, which regulates the activities of several enzymes and inhibits the phosphorylation of a variety of protein kinase C substrates in a calcium-dependent manner. The protein was recently found to activate a retinal membrane guanylate cyclase, and in this paper, we report that it inhibits the phosphorylation of an 80 kDa retinal protein (p80). Structurally, S100 beta consists of two EF-hands connected by a hinge region. In view of its small size, wide distribution in a variety of tissues, and regulation of many different proteins, it is of interest to identify the sites on the protein that interact with the effectors, and to determine if the same sites are responsible for interaction with different effectors. We addressed these questions with the use of synthetic peptides with sequences corresponding to different regions of S100 beta and testing their effects on the protein's activation of guanylate cyclase, and inhibition of p80 phosphorylation. Peptides with sequences corresponding to effector interaction sites were anticipated to either block or simulate the effects of S100 beta. The results show that two regions of S100 beta interact with effectors: the C-terminal region of Thr81-Glu91 and the hinge region of Leu32-Leu40. The synthetic peptide containing the latter sequence blocked the S100 beta activation of guanylate cyclase and inhibition of p80 phosphorylation, while the peptide containing the former sequence blocked cyclase activation and simulated S100 beta in inhibiting p80 phosphorylation. By determining the effects of including or excluding dithiothreitol in the assays, we observed that the cysteine residue in the C-terminal region of S100 beta (Cys84) participates in the regulation of guanylate cyclase but not of p80 phosphorylation. We conclude from these results that the C-terminal and hinge regions of S100 beta are important in the regulation of effector proteins and that Cys84 is essential for interaction with only specific effectors.