Introduction to Multiprocessor I/O Architecture

The computational performance of multiprocessors continues to improve by leaps and bounds, fueled in part by rapid improvements in processor and interconnection technology. I/O performance thus becomes ever more critical, to avoid becoming the bottleneck of system performance. In this paper we provide an introduction to I/O architectural issues in multiprocessors, with a focus on disk subsystems. While we discuss examples from actual architectures and provide pointers to interesting research in the literature, we do not attempt to provide a comprehensive survey. We concentrate on a study of the architectural design issues, and the effects of different design alternatives

Spasticity-assessment: a review

Study design:Review of the literature on the validity and reliability of assessment of spasticity and spasms.Objectives:Evaluate the most frequently used methods for assessment of spasticity and spasms, with particular focus on individuals with spinal cord lesions.Setting:Clinic for Spinal Cord Injuries, Rigshospitalet, University Hospital of Copenhagen, and Department of Medical Physiology, University of Copenhagen, Denmark.Methods:The assessment methods are grouped into clinical, biomechanical and electrophysiological, and the correlation between these is evaluated.Results:Clinical methods: For assessment of spasticity, the Ashworth and the modified Ashworth scales are commonly used. They provide a semiquantitative measure of the resistance to passive movement, but have limited interrater reliability. Guidelines for the testing procedures should be adhered to. Spasm frequency scales seem not to have been tested for reliability. Biomechanical methods such as isokinetic dynamometers are of value when an objective quantitative measure of the resistance to passive movement is necessary. They play a minor role in the daily clinical evaluation of spasticity. Electrophysiological methods: These techniques have provided valuable insight to the pathophysiological mechanisms involved in spasticity, but none of these techniques provide an easy and reliable assessment of spasticity for use in the daily clinic.Conclusion:A combination of electrophysiological and biomechanical techniques shows some promise for a full characterization of the spastic syndrome. There is a need of simple instruments, which provide a reliable quantitative measure with a low interrater variability

Structure-based discovery of opioid analgesics with reduced side effects

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids—which include fatal respiratory depression—are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21—a potent G(i) activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids