Although molecular dynamics (MD) simulations of biomolecular systems often run for days to months, many events of great scientific interest and pharmaceutical relevance occur on long time scales that remain beyond reach. We present several new algorithms and implementation techniques that significantly accelerate parallel MD simulations compared with current stateof-the-art codes. These include a novel parallel decomposition method and message-passing techniques that reduce communication requirements, as well as novel communication primitives that further reduce communication time. We have also developed numerical techniques that maintain high accuracy while using single precision computation in order to exploit processor-level vector instructions. These methods are embodied in a newly developed MD code called Desmond that achieves unprecedented simulation throughput and parallel scalability on commodity clusters. Our results suggest that Desmond's parallel performance substantially surpasses that of any previously described code. For example, on a standard benchmark, Desmond's performance on a conventional Opteron cluster with 2K processors slightly exceeded the reported performance of IBM's Blue Gene/L machine with 32K processors running its Blue Matter MD code.

LI E R. 1998. Sodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively) are widely used as cosmetic preservatives and general antimicrobial agents. They have been shown to be active against fungal cell walls, associated membranes and bacterial transport processes. Investigations were undertaken into the effect of these antimicrobial agents on substrate catabolism and intracellular ATP levels using an oxygen electrode and luciferin-luciferase technology, respectively. Results indicate that, while both compounds are poor inhibitors of substrate catabolism, sub-inhibitory concentrations of biocide greatly reduces intracellular ATP levels in both Escherichia coli NCIMB 10000 and Pseudomonas aeruginosa NCIMB 10548. This is thought to be due to the action of NaPT and ZnPT on the Gram-negative bacterial membrane. INTRODUCTIONSodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively, Fig. 1) are the sodium salt and zinc chelate of 1-hydroxy-2-pyridinethiol (Shaw et al. 1950 ;Albert et al. 1956 ;Hyde and Nelson 1984). Both NaPT and ZnPT have been shown to possess a wide spectrum of antimicrobial activity against fungal and bacterial species (Pansy et al. 1953 ;Albert et al. 1956 ;Hyde and Nelson 1984 ;Khattar et al. 1988). They are widely used as cosmetic preservatives (Nelson and Hyde 1981 ;Hyde and Nelson 1984) and are incorporated as anti-dandruff agents in shampoos (Fredriksin and Feargeman 1983 ;Hyde and Nelson 1984). They also possess excellent metal chelating properties and ZnPT is active as a metal complex (Davies 1985 ;Fenn and Alexander 1988).Previous work has suggested that this group of compounds is membrane active. This is indicated by the inhibition of uptake of several unrelated substrates in both bacteria and fungi (Chandler and Segel 1978;Friedman 1981;Khattar et al. 1988 ;Khattar and Salt 1993) and the observed depolarization of the transmembrane electrical potential in Neurospora crassa (Ermolayeva et al. 1995). The effects of an antimicrobial agent on substrate transport and related metabolism may be used as indicators of the membrane activity of the test agent (Gilbert et al. 1991). In turn, these effects may be reflected as a reduction in intracellular ATP levels (Harold Dundee, Bell Street, Dundee, DD1 1HG,.© 1998 The Society for Applied Microbiology 1972). Regardless of substrate transport, a direct membrane effect by a biocide may decrease intracellular ATP levels via disruption of the transmembrane proton motive force (PMF) and related processes. This has been exhibited with several membrane active agents including fentichlor, PHMB, alexidine and chlorhexidine (Bloomfield 1974 ;Chopra et al. 1987 ;Chawner and Gilbert 1989).This study describes the activity of NaPT and ZnPT on substrate transport and catabolism in Escherichia coli NCIMB 10000 and Pseudomonas aeruginosa NCIMB 10548 and the effects of these agents on bacterial intracellular ATP levels at sub-inhibitory and minimal inhibitory concentrations (MIC). MATERIALS AND METHODS Organisms and chemicalsStock cultures of Es...

Background: People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported. Methods: The Southall and Brent Revisited (SABRE) study is the UK largest tri-ethnic longitudinal cohort. Over 1400 surviving participants (58-85 y) attended the 2nd study-visit (2008-2011) during which comprehensive cardiovascular phenotyping, including 3D-echocardiography (3D-speckle-tracking (3D-STE)), computed tomography, coronary artery calcium scoring, pulse-wave velocity, central blood pressure, carotid artery ultrasound and retinal imaging were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people. Results: Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic-attendees). 3DE and 3D-STE were less feasible in this age group (76% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic-attendees). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility. Conclusions: Detailed cardiovascular phenotyping is feasible and reproducible in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases.

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