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At least 487 records · Page 27Linked to original sources
PubMed2003

Conceptual design of novel IP-conveyor-belt Weissenberg-mode data-collection system with multi-readers for macromolecular crystallography. A comparison between Galaxy and Super Galaxy.

Galaxy is a Weissenberg-type high-speed high-resolution and highly accurate fully automatic data-collection system using two cylindrical IP-cassettes each with a radius of 400 mm and a width of 450 mm. It was originally developed for static three-dimensional analysis using X-ray diffraction and was installed on bending-magnet beamline BL6C at the Photon Factory. It was found, however, that Galaxy was also very useful for time-resolved protein crystallography on a time scale of minutes. This has prompted us to design a new IP-conveyor-belt Weissenberg-mode data-collection system called Super Galaxy for time-resolved crystallography with improved time and crystallographic resolution over that achievable with Galaxy. Super Galaxy was designed with a half-cylinder-shaped cassette with a radius of 420 mm and a width of 690 mm. Using 1.0 A incident X-rays, these dimensions correspond to a maximum resolutions of 0.71 A in the vertical direction and 1.58 A in the horizontal. Upper and lower screens can be used to set the frame size of the recorded image. This function is useful not only to reduce the frame exchange time but also to save disk space on the data server. The use of an IP-conveyor-belt and many IP-readers make Super Galaxy well suited for time-resolved, monochromatic X-ray crystallography at a very intense third-generation SR beamline. Here, Galaxy and a conceptual design for Super Galaxy are described, and their suitability for use as data-collection systems for macromolecular time-resolved monochromatic X-ray crystallography are compared.

Crystallography, X-Ray↗
PubMed2002

Glycosylation of proteins: a computer based method for the rapid exploration of conformational space of N-glycans.

Inspection of protein databases suggests that as many as 70% of proteins have potential N-glycosylation sites. Unfortunately glycoproteins often refuse to crystallize and NMR techniques do not allow an unambiguous determination of the complete conformation of the sugar part. Therefore, time-consuming complex simulation methods are often used to explore the conformational space of N-glycans. The generation of a comprehensive data base describing the conformational space of larger fragments of N-glycans taking into account the effects of branching is presented. High-temperature molecular dynamics simulations of essential N-glycan fragments are performed until conformational equilibrium has been reached. Free energy landscapes are calculated for each glycosidic linkage. All possible conformations for each N-glycan fragment are automatically assigned, ranked according to their relative population and stored in a database. These values are recalled for the generation of a complete set of all possible conformations for a given N-glycan topology. The constructed conformations are ranked according to their energy content. Since this approach allows to explore the complete conformational space of a given N-glycan within a few minutes of CPU-time on a standard PC, it is well suited to be used as a Web-Based application.

Carbohydrate Conformation↗
PubMed1994

Magnetic resonance examination of the inner ear and cerebellopontine angle in patients with vertigo and/or abnormal findings at vestibular testing.

The inner ears of 167 patients with vertigo and/or abnormal findings at vestibular testing were studied using magnetic resonance (MR). Pathology potentially explaining vertigo was found in 54 patients, and was detected in the posterior fossa (28%), the internal auditory canal (28%) and the membranous labyrinth (44%). The overall percentage of pathology and the percentage of pathology found in the membranous labyrinth was high and was probably influenced by the referral pattern in our hospital where high resolution MR of the inner ear (three dimensional Fourier transformation-constructive interference in steady state sequence; 3DFT-CISS sequence) is available. Unenhanced, and especially gadolinium (Gd)-enhanced T1-weighted spin-echo images, are needed to detect most of the pathology inside the internal auditory canal, and some of the lesions inside the membranous labyrinth. 3DFT-CISS images are the only images that can show fibrous obliteration of the intralabyrinthine fluid spaces, and are therefore necessary to recognise most of the intralabyrinthine pathology. Finally, T2-weighted spin-echo images are best suited to demonstrate cerebellar or brain stem infarction. An additional MR-angiography sequence (three dimensional Fourier transformation-fast imaging with steady precession; 3DFT-FISP) is used when vascular compression of the cochleovestibular nerve is suspected. MR is the method of choice to look for pathology in patients with vertigo, and allows detection of pathology that remains invisible with other imaging techniques. However, well adapted sequences are needed to detect these lesions.

Cerebellopontine Angle↗
PubMed2006

A model of interprofessional informatics education.

An emphasis on patient safety and an administrative mandate to have information systems in place in most health care agencies in the USA by 2014 has put pressure on nursing informatics programs to increase the number of graduates. At the same time a need for change in health professions education was emphasized at an educational summit sponsored by the Institute of Medicine. Interprofessional education (IPE) will help to provide needed educational reform in informatics and is defined as planned occasions when two or more professions learn from each other and about each other in a structured manner. This paper discusses an evolving interprofessional (IPE) model of informatics education that has been developed at the University of Utah. Because of interprofessional collaboration, faculty, students, and support staff from both the medical and nursing informatics programs moved into a suite on the fifth floor of a state-of-art technology-rich health sciences education building. The co-located space has enabled the informatics programs to increase activities that promote interprofessional education.

Humans↗
PubMed1991

Physical characterization and crystallization of the carbohydrate-recognition domain of a mannose-binding protein from rat.

A portion of rat mannose-binding protein A (MBP-A), a Ca(2+)-dependent animal lectin, has been overproduced in a bacterial expression system, biochemically characterized, and crystallized. A fragment corresponding to the COOH-terminal 115 residues of native MBP-A, produced by subtilisin digestion of the bacterially expressed protein, contains the carbohydrate-recognition domain (CRD). Gel filtration, chemical cross-linking, and crystallographic self-rotation function analyses indicate that the subtilisin fragment is a dimer, although the complete bacterially expressed fragment, containing the neck and CRD of MBP-A, is a trimer. Crystals of the minimal CRD, obtained only as a complex with a Man6GlcNAc2Asn glycopeptide, diffract to Bragg spacings of at least 1.7 A. Several trivalent lanthanide ions (Ln3+) can substitute for Ca2+, as assessed by their ability to support carbohydrate binding and to protect the CRD from proteolysis in a manner similar to that observed for Ca2+. These assays indicate that Ln2+ binds about 30 times more tightly than Ca2+ to the CRD, and that two Ca2+ or Ln3+ bind to each monomer, a result confirmed by determination of the Ho3+ positions in a Ho(3+)-containing crystal of the CRD. Crystals grown in the presence of Ln3+ belong to different space groups from those obtained with Ca2+ and are therefore not useable for traditional crystallographic phase determination methods, but are well-suited for high resolution structure determination by multiwavelength anomalous dispersion phasing.

Animals↗
PubMed1982

Body composition measurements in normal man: the potassium, sodium, sulfate and tritium spaces in 58 adults.

The aqueous phase of total body composition varies with sex, and changes with age, necessitating age, sex and method-specific normal values. Consensus has developed for the methods most suited to clinical studies. 3H20 for water, 35SO4 for ECW, 24Na for NAc, and 40K for body potassium were used in 58 normal volunteers aged 19-80, 30 men and 28 women. This report shows significant age regressions in both sexes for total body water and intracellular water, and for both Na and K when referenced to body water. Combination of these findings with the highly age related decrease in total body potassium confirms previous studies that body cell mass decreases with age. Intracellular K+ and Na+ at the zero age intercept are 130 and 14.5 for males, and 124 and 24mEq/1 for females respectively. Secular decrease in K+ and increase in Na+ concentrations in the average cell are suggested although not established. Values for normal body composition, in subjects healthy by all available criteria are in some instances age and sex dependent, but in all parameters except fat show wide normal range (SD = 7% of mean) which derive more from biological variation than from limitations of measurement precision. However, use of body water rather than weight succeeds in narrowing this wide range, and is a more logical denominator which is readily subject to accurate measurement. In serial studies of the same subject, significant changes can be measured which are well within the normal range.

Adult↗
PubMed1997

Reduced space sequence alignment.

MOTIVATION: Sequence alignment is the problem of finding the optimal character-by-character correspondence between two sequences. It can be readily solved in O(n2) time and O(n2) space on a serial machine, or in O(n) time with O(n) space per O(n) processing elements on a parallel machine. Hirschberg's divide-and-conquer approach for finding the single best path reduces space use by a factor of n while inducing only a small constant slowdown to the serial version. RESULTS: This paper presents a family of methods for computing sequence alignments with reduced memory that are well suited to serial or parallel implementation. Unlike the divide-and-conquer approach, they can be used in the forward-backward (Baum-Welch) training of linear hidden Markov models, and they avoid data-dependent repartitioning, making them easier to parallelize. The algorithms feature, for an arbitrary integer L, a factor proportional to L slowdown in exchange for reducing space requirement from O(n2) to O(n1 square root of n). A single best path member of this algorithm family matches the quadratic time and linear space of the divide-and-conquer algorithm. Experimentally, the O(n1.5)-space member of the family is 15-40% faster than the O(n)-space divide-and-conquer algorithm.

Algorithms↗
PubMed1992

Crystallization of beta-galactosidase from Escherichia coli.

Two crystal forms of beta-galactosidase have been obtained from Escherichia coli. One crystal form is hexagonal space group P6222 or enantiomorph, with cell dimensions a = b = 154 A, c = 750 A. The second form is monoclinic, space group P21, with cell dimensions a = 107.9 A, b = 207.5 A, c = 509.9 A, beta = 94.7 degrees. The monoclinic form seems better suited to detailed structural analysis. The crystals are radiation-sensitive, but by using synchrotron radiation in conjunction with a long (400 mm) crystal-to-film distance it was possible to resolve the individual reflections. On the basis of crystal density measurements, there are four tetramers each of molecular weight 465,000 per asymmetric unit. The Patterson function strongly suggests that two of the tetramers are related to the other two by translation. The data are consistent with the tetramers having 222 point symmetry, but this is not proven.

Crystallography↗
PubMed1992

The holodent system, a new technique for measurement and storage of dental casts.

A system for producing holograms and for three-dimensional measuring on holograms is described. The precision of the system was evaluated when three-dimensional measurements were made on (1) a holographic image superimposed on the corresponding object and (2) two superimposed holographic images of the same object. When a metal test object with sharp well-defined contours, easy to reorientate was used, the precision was 0.02 to 0.11 mm for x, y, and z coordinates (transverse, longitudinal, and vertical planes). When dental casts that have less distinct contours were used, precision was reduced to 0.03 to 0.43 mm. Precision was high for the x and y coordinates and satisfactory for the z coordinate. The system has a precision that is equal to that of previously reported methods and may be well-suited for studies of dental positional changes in longitudinal materials of study models. Holograms of dental casts may solve storage problems by replacing space consuming plaster models.

Dental Records↗
PubMed1998

Microfluorometric analyses of glycogen in freshly dissected, single skeletal muscle fibres of the cane toad using a mechanically skinned fibre preparation.

The main objective of this study was to analyse glycogen in single muscle fibres, using a recently developed microfluorometric method which detects subpicomol amounts of NADPH, glucose and glycogen (as glucosyl units) (detection limit 0.16-0.17 pmol in a 25 nl sample) without fluorochrome amplification. The fibres were freshly dissected from the twitch region of the iliofibularis muscle of the cane toad (Bufo marinus), and were mechanically skinned under paraffin oil to gain access to the intracellular compartments. The results show that (1) glycogen concentrations in toad skeletal muscle fibres range between 25.8 and 369 mmol glucosyl units/litre fibre volume; (2) there is a large variation in glycogen content between individual fibres from the iliofibularis muscle of one animal; (3) there are seasonal differences in the glycogen content of toad single muscle fibres; (4) the total amount of glycogen in single muscle fibres of the toad does not decrease significantly when storing the tissue, under paraffin oil, at 20-25 degree C for up to 6 h or at 4 degree C for up to 24 h; and (5) 15-26% of fibre glycogen can be washed in an aqueous solution at pH 5-7, within 5 min, while 74-85% of fibre glycogen remains associated with the washed skinned fibre, even after 40 min exposure of the skinned fibre preparation to the aqueous environment. The retention of most glycogen in the fibre preparation after mechanical removal of the plasma membrane and extensive washing indicates that in toad skeletal muscle fibres the largest proportion of glycogen is tightly bound to intracellular structures. The results also show that the skinned muscle fibre preparation is well suited for microfluorometric glycogen determination, since low molecular weight non-glycogen contributors to the fluorescence signal can be removed from the myoplasmic space prior to the glycogen hydrolysis step.

Animals↗
PubMed2005

RNA backbone rotamers--finding your way in seven dimensions.

Despite the importance of local structural detail for a mechanistic understanding of RNA catalysis and binding functions, RNA backbone conformation has been recalcitrant to analysis. There are too many variable dihedral angles per residue, and their raw empirical distributions are poorly clustered. This study applies quality-filtering techniques (using resolution, crystallographic B factor and all-atom-steric clashes) to the backbone dihedral angle distributions from a selected 8636 residue RNA database. With noise levels significantly decreased, clear signal appears for the underlying angle preferences. We analyse the multidimensional backbone dihedral distributions within sugar-to-sugar 'suites' rather than chemical residues due to the greater base interaction and steric interdependence within the suite. The final result is a small library of RNA backbone rotamers, each represented by a data cluster in seven-dimensional dihedral space, which should provide valid conformations for nearly all RNA backbones encountered in experimental structures. We are in the process of improving that library, and developing tools and applications for it in structure determination and analysis.

Crystallography, X-Ray↗
PubMed1990

Evidence for positional coding in hyperacuity.

Observers performed simple pattern discriminations [tests of orientation (vernier) acuity and spatial-interval acuity] with targets consisting of spatially separated squares. We investigated the effects on acuity of supernumerary squares placed at various mean positions between the two squares constituting the target configuration. The exact position of the supernumerary squares relative to the target squares changed randomly from trial to trial, so that their spatial relationship to the targets could not serve as a cue. Observers attempted to ignore these supernumerary squares and to base their judgments on the outer target squares alone. The supernumerary squares raised thresholds if they were sufficiently close (4.4-arcmin separation) to the target squares but not if they were at a greater distance (21.0 arcmin). The results therefore show that the observers could ignore the supernumerary squares, even when they fell into the space between the target squares. This finding suggests that observers can select a class of length- and orientation-tuned filter that is suited exactly to the requirements of a particular psychophysical task. We argue that filter models of hyperacuity are insufficient unless they address this critical issue of filter selection and that a complete model requires an explicit spatial representation of target feature position.

Humans↗
PubMed2002

Extending the ALCOVE model of category learning to featural stimulus domains.

The ALCOVE model of category learning, despite its considerable success in accounting for human performance across a wide range of empirical tasks, is limited by its reliance on spatial stimulus representations. Some stimulus domains are better suited to featural representation, characterizing stimuli in terms of the presence or absence of discrete features, rather than as points in a multidimensional space. We report on empirical data measuring human categorization performance across a featural stimulus domain and show that ALCOVE is unable to capture fundamental qualitative aspects of this performance. In response, a featural version of the ALCOVE model is developed, replacing the spatial stimulus representations that are usually generated by multidimensional scaling with featural representations generated by additive clustering. We demonstrate that this featural version of ALCOVE is able to capture human performance where the spatial model failed, explaining the difference in terms of the contrasting representational assumptions made by the two approaches. Finally, we discuss ways in which the ALCOVE categorization model might be extended further to use "hybrid" representational structures combining spatial and featural components.

Discrimination Learning↗
PubMed2000

A candidate pathway for a visual instructional signal to the barn owl's auditory system.

Many organisms use multimodal maps to generate coherent neuronal representations that allow adequate responses to stimuli that excite several sensory modalities. During ontogeny of these maps, one modality typically acts as the dominant system the other modalities are aligned to. A well studied model for the alignment of sensory maps is the calibration of the auditory space map by the visual system in the optic tectum of the barn owl. However, a projection from the optic tectum to the site of plasticity in the auditory pathway that could deliver an instructive signal has not been found so far. We have analyzed the development of the connectivity between the bimodal (visual and auditory) map of space in the barn owl's optic tectum and the auditory space map in the inferior colliculus with tracing methods and intracellular fills. Neurons in the tectal stratum griseum centrale were found to be suited to deliver an alignment signal from the visual midbrain to the auditory pathway. These neurons are presumably part of the efferent tectal projection pathway that mediates head saccades. The implications of a sensory alignment signal possibly being delivered by a (pre)motor command pathway are discussed.

Animals↗
PubMed1994

Multipoint K-space point mapping (KPM) technique for NMR microscopy.

An extended version of point mapping in k-space for microscopic imaging applications is analyzed and described. Because the method can offer a number of advantages over the other conventional techniques due to the short echo time (TE), the technique is ideally suited for microscopic imaging where field inhomogeneity dependent signal degradation is one of the main causes of image resolution degradation (1-3). Another application area is the case of imaging in a highly inhomogeneous situation such as the fringe field imaging (Z.H. Cho, E. Wong, U.S. Patent #5023554 (1990). The first original point mapping technique described by Nauert et al. (1) and Emid and Creyghton (2) is analyzed as a k-space point mapping technique, and the original technique is extended to a multipoint k-space point mapping (MKPM) technique. With the extended MKPM technique, much faster microscopic imaging that is free of susceptibility and diffusion effects can be performed (4-6). To examine this idea, computer simulations are performed and their results are given.

Magnetic Resonance Spectroscopy↗
PubMed1991

Exciton microscopy and reaction kinetics in restricted spaces.

We describe the development of a new biologically non-invasive ultraresolution light microscopy, based on combining the energy transfer "spectral ruler" method with the micro-movement technology employed in scanning tunneling microscopy (STM). We use near-field scanning optical microscopy, with micropipettes containing crystals of energy packaging donor molecules in the tips that can have apertures below 5 nm. The excitation of these tips extends near field microscopy well beyond the 50 nm limit. The theoretical resolution limit for this spectrally sensitive light microscopy is well below 1 nm. Exciton microscopy is ideally suited for kinetic studies that are spatially resolved on the molecular scale, i.e., at a single molecule site. Moreover, the successful operation of the scanning exciton tip depends on an understanding of reaction kinetics in restricted spaces. In contrast to the many recent reviews on scanning tip microscopies, there is no adequate review of the recent revolutionary developments in the area of reaction kinetics in confined geometries. We thus attempt such a review in this paper. Reactions in restricted spaces rarely get stirred vigorously by convection and are thus often controlled by diffusion. Furthermore, the compactness of the Brownian motion leads to both anomalous diffusion and anomalous reaction kinetics. Elementary binary reactions of the type A + A----Products, A + B----Products and A + C----C + Products are discussed theoretically for both batch and steady-state conditions. The anomalous reaction orders and time exponents (for the rate coefficients) are discussed for various situations. Global and local rate laws are related to particle distribution functions. Only Poissonian distributions guarantee the classical rate laws. Reactant self-organization leads to interesting new phenomena. These are demonstrated by theory, simulations, and experiments. The correlation length of reactant production affects the self-ordering length-scale. These effects are demonstrated experimentally, including the stability of reactant segregation observed in chemical reactions in one-dimensional spaces, e.g., capillaries and microcapillaries. The gap between the reactant A (cation) and B (anion) actually increases in time, and extends over millimeters. Excellent agreement is found among theory, simulation, and experiment for the various scaling exponents.

Kinetics↗
PubMed2005

Toward a new paradigm in hospital-based pediatric education: the development of an onsite simulator program.

OBJECTIVE: The low incidence of crises in pediatrics, coupled with logistic issues and restricted work hours for trainees, hinders opportunities for frequent practice of crisis management and teamwork skills. We hypothesized that a dedicated simulator suite contiguous to the intensive care unit (ICU) would enhance the frequency and breadth of critical-incident training for a range of clinicians. DESIGN: Descriptive study. SETTING: A tertiary-care pediatric teaching hospital. MEASUREMENTS AND MAIN RESULTS: A realistic pediatric simulator suite was constructed 100 feet from the ICU, at a total base cost of $290,000. The simulation room is an exact replica of an ICU bed space, incorporating high-fidelity mannequin simulators. To capture an even wider audience, a portable unit was also created. Leaders from seven departments-critical care, cardiac intensive care, emergency medicine, transport medicine, anesthesia, respiratory care, and general pediatrics-completed instructor training to ensure effective debriefing techniques. Pediatric staff, including 100% of critical care fellows, 86% of nurses, 90% of respiratory therapists, and 74% of pediatric house staff, participated in >1500 learning encounters per year. All individuals were trained during their normal workday in the hospital. Courses in crisis resource management, skills acquisition, annual review, orientation, and trauma management (1,116, 98, 90, 60, and 60 encounters per year, respectively) were all designed by a multidisciplinary committee to ensure goal-directed education to a range of audiences. Annual costs were on par with those at other centers (approximately 44 dollars per trainee encounter). CONCLUSIONS: An onsite and comprehensive simulation program can significantly increase the opportunities for clinicians from multiple disciplines, in the course of their daily routines, to repetitively practice responses to pediatric medical crises. After an initial capital investment, the training appears to be cost-effective. Hospital-based simulator suites may point the way forward as a new paradigm for the effective education of today's busy clinicians.

Clinical Competence↗