An introduction to stereochemical restraints

A brief summary of the types of restraint defined in refinement dictionaries

Journal publishing with Acrobat: the CAJUN project

The publication of material in electronic form should ideally preserve, in a unified document representation, all of the richness of the printed document while maintaining enough of its underlying structure to enable searching and other forms of semantic processing. Until recently it has been hard to find a document representation which combined these attributes and which also stood some chance of becoming a de facto multi-platform standard. This paper sets out experience gained within the Electronic Publishing Research Group at the University of Nottingham in using Adobe Acrobat software and its underlying PDF (Portable Document Format) notation. The CAJUN project1 (CD-ROM Acrobat Journals Using Networks) began in 1993 and has used Acrobat software to produce electronic versions of journal papers for network and CD-ROM dissemination. The paper describes the project's progress so far and also gives a brief assessment of PDF's suitability as a universal document interchange standard

Single-Bottleneck Approximation for Driven Lattice Gases with Disorder and Open Boundary Conditions

We investigate the effects of disorder on driven lattice gases with open boundaries using the totally asymmetric simple exclusion process as a paradigmatic example. Disorder is realized by randomly distributed defect sites with reduced hopping rate. In contrast to equilibrium, even macroscopic quantities in disordered non-equilibrium systems depend sensitively on the defect sample. We study the current as function of the entry and exit rates and the realization of disorder and find that it is, in leading order, determined by the longest stretch of consecutive defect sites (single-bottleneck approximation, SBA). Using results from extreme value statistics the SBA allows to study ensembles with fixed defect density which gives accurate results, e.g. for the expectation value of the current. Corrections to SBA come from effective interactions of bottlenecks close to the longest one. Defects close to the boundaries can be described by effective boundary rates and lead to shifts of the phase transitions. Finally it is shown that the SBA also works for more complex models. As an example we discuss a model with internal states that has been proposed to describe transport of the kinesin KIF1A.Comment: submitted to J. Stat. Mec

Importance of the pleckstrin homology domain of dynamin in clathrin-mediated endocytosis

AbstractThe GTPase dynamin plays an essential role in clathrin-mediated endocytosis [1–3]. Substantial evidence suggests that dynamin oligomerisation around the necks of endocytosing vesicles and subsequent dynamin-catalysed GTP hydrolysis is responsible for membrane fission [4,5]. The pleckstrin homology (PH) domain of dynamin has previously been shown to interact with phosphoinositides, but it has not been determined whether this interaction is essential for dynamin's function in endocytosis [6–9]. In this study, we address the in vivo function of the PH domain of dynamin by assaying the effects of deletions and point mutations in this region on transferrin uptake in COS-7 fibroblasts. Overexpression of a dynamin construct lacking its entire PH domain potently blocked transferrin uptake, as did overexpression of a dynamin construct containing a mutation in the first variable loop of the PH domain. Structural modelling of this latter mutant suggested that the lysine residue at position 535 (Lys535) may be critical in the coordination of phosphoinositides, and indeed, the purified mutant no longer interacted with lipid nanotubes. Interestingly, the inhibitory phenotype of cells expressing this dynamin mutant was partially relieved by a second mutation in the carboxy-terminal proline-rich domain (PRD), one that prevents dynamin from binding to the Src homology 3 (SH3) domain of amphiphysin. These data demonstrate that dynamin's interaction with phosphoinositides through its PH domain is essential for endocytosis. These findings also support our hypothesis that PRD–SH3 domain interactions are important in the recruitment of dynamin to sites of endocytosis

Creating a Realistic Weather Environment for Motion-Based Piloted Flight Simulation

A flight simulation environment is being enhanced to facilitate experiments that evaluate research prototypes of advanced onboard weather radar, hazard/integrity monitoring (HIM), and integrated alerting and notification (IAN) concepts in adverse weather conditions. The simulation environment uses weather data based on real weather events to support operational scenarios in a terminal area. A simulated atmospheric environment was realized by using numerical weather data sets. These were produced from the High-Resolution Rapid Refresh (HRRR) model hosted and run by the National Oceanic and Atmospheric Administration (NOAA). To align with the planned flight simulation experiment requirements, several HRRR data sets were acquired courtesy of NOAA. These data sets coincided with severe weather events at the Memphis International Airport (MEM) in Memphis, TN. In addition, representative flight tracks for approaches and departures at MEM were generated and used to develop and test simulations of (1) what onboard sensors such as the weather radar would observe; (2) what datalinks of weather information would provide; and (3) what atmospheric conditions the aircraft would experience (e.g. turbulence, winds, and icing). The simulation includes a weather radar display that provides weather and turbulence modes, derived from the modeled weather along the flight track. The radar capabilities and the pilots controls simulate current-generation commercial weather radar systems. Appropriate data-linked weather advisories (e.g., SIGMET) were derived from the HRRR weather models and provided to the pilot consistent with NextGen concepts of use for Aeronautical Information Service (AIS) and Meteorological (MET) data link products. The net result of this simulation development was the creation of an environment that supports investigations of new flight deck information systems, methods for incorporation of better weather information, and pilot interface and operational improvements for better aviation safety. This research is part of a larger effort at NASA to study the impact of the growing complexity of operations, information, and systems on crew decision-making and response effectiveness; and then to recommend methods for improving future designs

The mononuclear metal center of type-I dihydroorotase from aquifex aeolicus

Abstract Background Dihydroorotase (DHO) is a zinc metalloenzyme, although the number of active site zinc ions has been controversial. E. coli DHO was initially thought to have a mononuclear metal center, but the subsequent X-ray structure clearly showed two zinc ions, α and β, at the catalytic site. Aquifex aeolicus DHO, is a dodecamer comprised of six DHO and six aspartate transcarbamoylase (ATC) subunits. The isolated DHO monomer, which lacks catalytic activity, has an intact α-site and conserved β-site ligands, but the geometry of the second metal binding site is completely disrupted. However, the putative β-site is restored when the complex with ATC is formed and DHO activity is regained. Nevertheless, the X-ray structure of the complex revealed a single zinc ion at the active site. The structure of DHO from the pathogenic organism, S. aureus showed that it also has a single active site metal ion. Results Zinc analysis showed that the enzyme has one zinc/DHO subunit and the addition of excess metal ion did not stimulate catalytic activity, nor alter the kinetic parameters. The metal free apoenzyme was inactive, but the full activity was restored upon the addition of one equivalent of Zn2+ or Co2+. Moreover, deletion of the β-site by replacing the His180 and His232 with alanine had no effect on catalysis in the presence or absence of excess zinc. The 2.2 Å structure of the double mutant confirmed that the β-site was eliminated but that the active site remained otherwise intact. Conclusions Thus, kinetically competent A. aeolicus DHO has a mononuclear metal center. In contrast, elimination of the putative second metal binding site in amidohydrolyases with a binuclear metal center, resulted in the abolition of catalytic activity. The number of active site metal ions may be a consideration in the design of inhibitors that selectively target either the mononuclear or binuclear enzymes

An introduction to data reduction: space-group determination, scaling and intensity statistics

A summary of how to run the data-reduction programs in the CCP4 suite