Structuring diagnostic knowledge for large-scale process systems

A set of guidelines is described for generating an initial organization of knowledge for distributed diagnosis of a process plant. The diagnostic knowledge is organized hierarchically by primary processing systems (commonly feed, reaction, and separation in chemical plants), subsystems, components, behaviors and malfunction modes. The resulting classification hierarchy decomposes the diagnostic problem solving into coordinated, distributed modules, where different modules may use different methods to address specific local subproblems. Classification hierarchies, organized in this way, provide effective modularity for organizing large-scale, knowledge-based diagnostic systems, which are difficult to construct without pertinent organizing principles. Such hierarchies provide a framework for systematic knowledge acquisition and maintenance. Application of the guidelines emphasizes readily available sources of knowledge, considers common design and operating objectives of process plants, draws upon operating expertise and builds on generic process characteristics. Application is illustrated for a fluidized catalytic cracking unit and a paraxylene production unit.     

Interview reliability for assessing mental work demands.

This study presented and evaluated an interview method for the analysis of tasks included in a work situation. What mental demands and possibilities do the work tasks give rise to? When was the work more or less automatic? When was use of active knowledge required? When were problem solving and planning needed? The study included an assessment of the interobserver reliability of the interviews with employees from 5 different careers: bus drivers (n?=?10), home service workers (n?=?32), carpenters (n?=?11), farmers (n?=?14), and teachers (n?=?26). The extent to which this method can be reproduced in studies of different occupations is discussed. The interobserver reliability was good (.75–.82). There is support for the stability and usefulness of the interview for most types of work concerning the 3 categories of mental demands: routine, active knowledge, and problem solving/creativity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and Preliminary Evaluation of 11C-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M₁–M₅) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M₁/M₄-preferring agonist, in patients of schizophrenia and Alzheimer's disease, M₁- or M₄-selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of ¹¹C-labeled positron emission tomography (PET) ligands based on a validated M₄R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [¹¹C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay-corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol⁻¹). In vitro autoradiography studies indicated that these three ligands possess moderate-to-high in vitro specific binding to M₄R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.     

Transport of surface-modified nanoparticles through cell monolayers

We synthesized three peptides, a D-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, Peff, of all six materials through CaCo-2 monolayers. The transport of peptide-nanoparticles was characterized by a lag phase (0-8 h) and a steady-state phase (9-27 h). The steady-state Peff values for peptides were in the order r8(FITC)>Tat(FITC)=Cp(FITC). When r8(FITC) and Tat(FITC) peptides were attached to the nanoparticle, they conferred their propensity to traverse cell monolayers onto the nanoparticle, whereas Cp(FITC) did not. Thus, when the r8(FITC) peptide was attached to the amino-CLIO nanoparticle, the resulting peptide-nanoparticle had a Peff similar to that of this poly-D-arginyl peptide alone. The Peff of r8(FITC)-CLIO (MW approximately 1000 kDa) was similar to that of mannitol (MW=182 Da), a poorly transported reference substance, with a far lower molecular weight. These results are the first to indicate that the modification of nanoparticles by attachment of membrane-translocating sequence-based peptides can alter nanoparticle transport through monolayers. This suggests that the surface modification of nanoparticles might be a general strategy for enhancing the permeability of drugs and that high-permeability nanoparticle-based therapeutics can be useful in selected pharmaceutical applications.     

The causes and costs of defects in construction: A study of seven building projects

To perform rational defect prevention, it is necessary to have knowledge about defects, their causes and associated costs. The purpose of the study presented here is to stimulate improvements by indicating where preventive measures are most effective as well as how to perform them. A study of defects in construction was performed during the period 1986–1990. A new and deeper study has been performed by the same research group during 1994–1996. Seven building projects have each been monitored during a 6 month-period. Observers spent 8 h a day at the site analysing and describing defects occurring. A total of 2879 defects have been collected and fully described, including their root causes. Formal interviews with 92 key persons have been made.     

Synthesis and Preliminary Evaluation of [11C]GNE-1023 as a Potent PET Probe for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2) in Parkinson's Disease

Leucine-rich repeat kinase 2 (LRRK2) is a large protein involved in the pathogenesis of Parkinson's disease (PD). It has been demonstrated that PD is mainly conferred by LRRK2 mutations that bring about increased kinase activity. As a consequence, selective inhibition of LRRK2 may help to recover the normal functions of LRRK2, thereby serving as a promising alternative therapeutic target for PD treatment. The mapping of LRRK2 by positron emission tomography (PET) studies allows a thorough understanding of PD and other LRRK2-related disorders; it also helps to validate and translate novel LRRK2 inhibitors. However, no LRRK2 PET probes have yet been reported in the primary literature. Herein we present a facile synthesis and preliminary evaluation of [¹¹C]GNE-1023 as a novel potent PET probe for LRRK2 imaging in PD. [¹¹C]GNE-1023 was synthesized in good radiochemical yield (10 % non-decay-corrected RCY), excellent radiochemical purity (>99 %), and high molar activity (>37 GBq μmol⁻¹). Excellent in vitro binding specificity of [¹¹C]GNE-1023 toward LRRK2 was demonstrated in cross-species studies, including rat and nonhuman primate brain tissues by autoradiography experiments. Subsequent whole-body biodistribution studies indicated limited brain uptake and urinary and hepatobiliary elimination of this radioligand. This study may pave the way for further development of a new generation of LRRK2 PET probes.     

Television violence and children's aggression: Testing the priming, social script, and disinhibition predictions.

The effect of television violence on boys' aggression was investigated with consideration of teacher-rated characteristic aggressiveness, timing of frustration, and violence-related cues as moderators. Boys in Grades 2 and 3 (N?=?396) watched violent or nonviolent TV in groups of 6, and half the groups were later exposed to a cue associated with the violent TV program. They were frustrated either before or after TV viewing. Aggression was measured by naturalistic observation during a game of floor hockey. Groups containing more characteristically high-aggressive boys showed higher aggression following violent TV plus the cue than following violent TV alone, which in turn produced more aggression than did the nonviolent TV condition. There was evidence that both the violent content and the cue may have suppressed aggression among groups composed primarily of boys low in characteristic aggressiveness. Results were interpreted in terms of current information-processing theories of media effects on aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coronary sinus pacing prevents induction of atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is due to reentry, and its incidence has been shown to decrease after dual-site atrial or biatrial pacing. We investigated whether a simpler pacing approach via the distal coronary sinus (CSd) could eliminate AF inducibility by high right atrial (HRA) extrastimuli (APDs). We based our hypothesis on our previous observation that AF inducibility by HRA APDs was associated with conduction delays to the posterior triangle of Koch, whereas AF was never induced with CSd APDs, which were associated with minimal intra-atrial conduction delays. METHODS AND RESULTS: Programmed electrical stimulation was performed from the high right atrium and CSd, and bipolar recordings were obtained from the high right atrium, His bundle, posterior triangle of Koch, and coronary sinus. In 13 patients (age, 44+/-18 years), AF was reproducibly induced with a critically timed HRA APD (220+/-22 ms) delivered during HRA pacing. AF was not induced in any of the patients when HRA APDs were delivered during CSd pacing at the same critical coupling intervals. Coronary sinus APDs delivered during HRA pacing also were not associated with AF induction. The APD coupling interval measured at the posterior triangle of Koch during CSd pacing was significantly prolonged compared with the one measured during HRA pacing and AF induction (381+/-58 versus 263+/-37 ms; P<.0001). CONCLUSIONS: We propose that CSd pacing suppresses the propensity of HRA APDs to induce AF by limiting their prematurity at the posterior triangle of Koch and not allowing local conduction delay and local reentry to occur.