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" It must be remembered that there is nothing more difficult to plan, more doubtful of success, nor more dangerous to manage than the creation of a new system. For the initiator has the enmity of all who would profit by the preservation of the old institution and merely lukewarm defenders in those who would gain by the new ones "-Machiavelli, " The Prince,(More)
The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases. Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity(More)
MS73 is one of a family of ATPases that act as regulatory subunits of the 26S proteasome. Localisation of this ATPase in histological sections of hippocampus from Alzheimer's disease (AD) and in cingulate gyrus sections of dementia with Lewy bodies (DLB) brains was examined immunohistochemically. In all cases of AD (n = 10) neurofibrillary tangles (NFT),(More)
For all the rapid advances in computer hardware and specific software technology, enterprise engineering, reengineering, and enterprise integration efforts continue to lack effective, widely understood methods for engineering large-scale information systems. Diverse methods are needed to engineer systems that exhibit desirable life-cycle characteristics(More)
We purified by fractionation on 10-40% glycerol gradients, 26S proteasomes from normal human spermatozoa. These proteasomes, which participate in the ATP-dependent degradation of ubiquitinated proteins, share a similar sedimentation coefficient to those purified from other human tissues. Fluorogenic peptide assays reveal they have chymotrypsin, trypsin and(More)
Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S(More)
The purpose of this article is to serve as a clear introduction to the modeling languages of the three most widely used IDEF methods: IDEF0, IDEF1X, and IDEF3. Each language is presented in turn, beginning with a discussion of the underlying " ontology " the language purports to describe, followed by presentations of the syntax of the language —(More)
In Alzheimer's disease (AD) neurofibrillary tangles (NFT) are strongly tau and ubiquitin immunopositive, and contain an aberrant form of ubiquitin derived from the ubiquitin-B gene denoted as UBB+1. We explored whether the tau-related NFT seen in another neurodegenerative disease, progressive supranuclear palsy (PSP), also showed an accumulation of UBB+1.(More)