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PubMed2006

A probabilistic approach to protein backbone tracing in electron density maps.

One particularly time-consuming step in protein crystallography is interpreting the electron density map; that is, fitting a complete molecular model of the protein into a 3D image of the protein produced by the crystallographic process. In poor-quality electron density maps, the interpretation may require a significant amount of a crystallographer's time. Our work investigates automating the time-consuming initial backbone trace in poor-quality density maps. We describe ACMI (Automatic Crystallographic Map Interpreter), which uses a probabilistic model known as a Markov field to represent the protein. Residues of the protein are modeled as nodes in a graph, while edges model pairwise structural interactions. Modeling the protein in this manner allows the model to be flexible, considering an almost infinite number of possible conformations, while rejecting any that are physically impossible. Using an efficient algorithm for approximate inference--belief propagation--allows the most probable trace of the protein's backbone through the density map to be determined. We test ACMI on a set of ten protein density maps (at 2.5 to 4.0 A resolution), and compare our results to alternative approaches. At these resolutions, ACMI offers a more accurate backbone trace than current approaches.

Algorithms↗

PubMed2000

Towards the cloning of GLY1.

The Arabidopsis mutants designated gly1 exhibit a reduced carbon flux through the prokaryotic pathway that is compensated for by an increased carbon flux through the eukaryotic pathway. Biochemical approaches reveal that the gly1 phenotype cannot be explained by a deficiency in the enzymes of the prokaryotic pathway. The chemical complementation of the mutant phenotype by exogenous glycerol treatment of gly1 plants suggests a lesion affecting the glycerol 3-phosphate supply within the chloroplast. As an alternative to the biochemical study of the gly1 mutants we set out to map the GLY1 locus. The gly1 mutant being an EMS (ethyl methane sulphonate) mutant, we used a strategy based on the polymorphism existing between Arabidopsis ecotypes, here Columbia (gly1 background) and Landsberg erecta. We mapped gly1 on chromosome II. During the process of chromosome walking, the complete sequence of chromosome II was released, allowing us to make assumptions on candidate genes based on map location. We are currently sequencing the putative genes.

Arabidopsis↗

PubMed1976

Correlations between the spread of ventricular activation and map patterns of measured and difference maps.

Three kinds of torso surface isopotential maps (measured, simulated, and difference maps) were delineated at every 1.5 (or 3) msec. during the QRS duration from the 85 unipolar lead ECG's led from the surface of a cylindrical torso model filled with perfusate and containing a canine heart undergoing Langendorff's perfusion. These three maps were compared as to the propagation process of ventricular activation obtained from the same heart and close correlations were found between the spread of ventricular activation and the map patterns of measured and difference maps. The difference map mainly reflected the proximity potential at each instant of ventricular activation in QRS duration and, when used in combination with the measured map, it was useful to estimate the spread of ventricular activation, especially around the stage of epicardial breakthrough of the activation front. It was confirmed that the interpretation of the difference map expressed in the present paper would not be misleading even if applied to a difference map obtained in a human torso model experiment.

Action Potentials↗

PubMed1998

On the interaction of numerical and size information in digit comparison: a behavioral and event-related potential study.

To investigate effects of dimensional congruity in digit comparison processes we recorded response latencies, error rates and event-related potentials (ERPs) in a situation when the relevant and the irrelevant dimension of judgement, the digit's physical size or its numerical value, varied unpredictably from trial to trial. Congruity effects may arise at early processing stages, where both numerical and size information are mapped onto a common, integrated representation. Alternatively, numerical and size information may be processed in functionally independent channels and interact only at a later stage of response activation. For both, numerical and size comparisons, reliable distance effects on ERPs (starting 224 ms post-stimulus at frontal electrode sites) and on behavioral data were observed. Congruity effects follow a timecourse that mirror-images the temporal pattern found for the distance effects: while distance effects on difference potentials start about 64 ms earlier for numerical comparisons, congruity effects due to the irrelevant attribute are seen about 88 ms earlier for size comparisons. While Lateralized Readiness Potentials (LRPs) for incongruent trials are shifted in time, there was no indication of an activation for the incorrect response in incongruent trials, as an account of congruity effects in terms of response competition would predict. The most parsimonious explanation of our results is that numerical and size information are extracted in parallel, are both converted into an integrated representation and potentially interact during these early parallel stages.

Adult↗

PubMed2005

Fuzzy-rule-based image reconstruction for positron emission tomography.

Positron emission tomography (PET) and single-photon emission computed tomography have revolutionized the field of medicine and biology. Penalized iterative algorithms based on maximum a posteriori (MAP) estimation eliminate noisy artifacts by utilizing available prior information in the reconstruction process but often result in a blurring effect. MAP-based algorithms fail to determine the density class in the reconstructed image and hence penalize the pixels irrespective of the density class. Reconstruction with better edge information is often difficult because prior knowledge is not taken into account. The recently introduced median-root-prior (MRP)-based algorithm preserves the edges, but a steplike streaking effect is observed in the reconstructed image, which is undesirable. A fuzzy approach is proposed for modeling the nature of interpixel interaction in order to build an artifact-free edge-preserving reconstruction. The proposed algorithm consists of two elementary steps: (1) edge detection, in which fuzzy-rule-based derivatives are used for the detection of edges in the nearest neighborhood window (which is equivalent to recognizing nearby density classes), and (2) fuzzy smoothing, in which penalization is performed only for those pixels for which no edge is detected in the nearest neighborhood. Both of these operations are carried out iteratively until the image converges. Analysis shows that the proposed fuzzy-rule-based reconstruction algorithm is capable of producing qualitatively better reconstructed images than those reconstructed by MAP and MR P algorithms. The reconstructed images a resharper, with small features being better resolved owing to the nature of the fuzzy potential function.

Algorithms↗

PubMed2006

American Dietetic Association's Standardized Nutrition Language: Project logic model and current status.

Standardized terminology and digital sources of evidence are essential for evidence-based practice. Dieticians desire concise and consistent documentation of nutrition diagnoses, interventions and outcomes that will be fit for electronic health records. Building on more than 5 years of work to generate the Nutrition Care Process and Model as a road map to quality nutrition care and outcomes, and recognizing existing standardized languages serving other health professions, a task force of the American Dietetic Association (ADA) has begun to develop and disseminate standardized nutrition language. This paper will describe the group's working logic model, the Nutrition Care Process, and the current status of the nutrition language with comparisons to nursing process and terminology.

Dietetics↗

PubMed2003

Comparison of minisatellites.

In the class of repeated sequences that occur in DNA, minisatellites have been found polymorphic and became useful tools in genetic mapping and forensic studies. They consist of a heterogeneous tandem array of a short repeat unit. The slightly different units along the array are called variants. Minisatellites evolve mainly through tandem duplications and tandem deletions of variants. Jeffreys et al. (1997) devised a method to obtain the sequence of variants along the array in a digital code and called such sequences maps. Minisatellite maps give access to the detail of mutation processes at work on such loci. In this paper, we design an algorithm to compare two maps under an evolutionary model that includes deletion, insertion, mutation, tandem duplication, and tandem deletion of a variant. Our method computes an optimal alignment in reasonable time; and the alignment score, i.e., the weighted sum of its elementary operations, is a distance metric between maps. The main difficulty is that the optimal sequence of operations depends on the order in which they are applied to the map. Taking the maps of the minisatellite MSY1 of 609 men, we computed all pairwise distances and reconstructed an evolutionary tree of these individuals. MSY1 (DYF155S1) is a hypervariable locus on the Y chromosome. In our tree, the populations of some haplogroups are monophyletic, showing that one can decipher a microevolutionary signal using minisatellite maps comparison.

Algorithms↗

PubMed1988

Astrocytes synthesize angiotensinogen in brain.

Cell types associated with angiotensinogen mRNA in rat brain were identified in individual brain sections by in situ hybridization with tritiated RNA probes or with a sulfur-35--labeled oligonucleotide combined with immunocytochemical detection of either glial fibrillary acidic protein (GFAP) for astrocytes or microtubule-associated protein (MAP-2) for neurons. Autoradiography revealed silver grains clustered primarily over GFAP-reactive soma and processes; most grain clusters were not associated with MAP-2--reactive cells. These results demonstrate that, in contrast to other known neuropeptide precursors, angiotensinogen is synthesized by glia.

Angiotensinogen↗

PubMed1999

Creation and use of a Talairach-compatible atlas for accurate, automated, nonlinear intersubject registration, and analysis of functional imaging data.

Spatial normalization in functional imaging can encompass various processes, including nonlinear warping to correct for intersubject differences, linear transformations to correct for identifiable head movements, and data detrending to remove residual motion correlated artifacts. We describe the use of AIR to create a custom, site-specific, normal averaged brain atlas that can be used to map T2 weighted echo-planar images and coplanar functional images directly into a Talairach-compatible space. We also discuss extraction of characteristic descriptors from sets of linear transformation matrices describing head movements in a functional imaging series. Scores for these descriptors, derived using principal components analysis with singular value decomposition, can be treated as confounds associated with each individual image in the series and systematically removed prior to voxel-by-voxel statistical analysis.

Anatomy, Artistic↗

PubMed2004

Does computation provide a model for creativity? An epistemological perspective in neuroscience.

In 1939 Alan Turing, a major scholar in the field of mechanical computation, described a system whose computational power was beyond that of a discrete, finite state machine (Turing Machine). The composition of this system was likely the first example of what is now called an hybrid computational system. Since then, development of neural networks and brain automata has made aware that forms of computation might exist that are likely to go beyond Turing's limits. Natural systems, like the central nervous system in Mammals and man, are likely to use such a type of computation, especially to perform highly integrating activities, like feedback controls and mental creative processes. The latter are usually understood as processes that involve infinitary procedures, ending up in a complex information network, the computational maps, in which both digital, Turing-like computation and continuous, analog forms of calculus are expected to occur. Pictorial representation may be a fruitful example, mostly metaphorical, to analyze the use of this hybrid forms of computation by higher order computational maps, and the possible role of these types of computational processes in painting creativity is briefly analyzed in comparing 15th vs 16th century Renaissance Art. An open challenge for neuroscience in the 21st century is to clarify whether a hybrid neural learning network might represent a reasonable clue to scientifically interpret the theme of "creativity".

Art↗

PubMed2006

Condensation transitions in a model for a directed network with weighted links.

An exactly solvable model for the rewiring dynamics of weighted, directed networks is introduced. Simulations indicate that the model exhibits two types of condensation: (i) a phase in which, for each node, a finite fraction of its total out-strength condenses onto a single link; (ii) a phase in which a finite fraction of the total weight in the system is directed into a single node. A virtue of the model is that its dynamics can be mapped onto those of a zero-range process with many species of interacting particles--an exactly solvable model of particles hopping between the sites of a lattice. This mapping, which is described in detail, guides the analysis of the steady state of the network model and leads to theoretical predictions for the conditions under which the different types of condensation may be observed. A further advantage of the mapping is that, by exploiting what is known about exactly solvable generalizations of the zero-range process, one can infer a number of generalizations of the network model and dynamics which remain exactly solvable.

Journal Article↗

PubMed1998

Bifurcation properties of the two process model.

Daan's two process model is known to be one of the most powerful models, covering various situations from free-running to sleep deprivation. In this study, bifurcation properties of the model dynamics as function of a gap, D, between the threshold processes are clarified using a circle map. As a function of D, we will show that the model has the different types of the mutual entrainment regions that are intervened by the tangent bifurcation. The variable behavior of human circadian rhythm is suggested to be systematically understood based on the bifurcation properties of the two process model.

Cerebral Cortex↗

PubMed2001

Dynamic organization of the somatosensory cortex induced by motor activity.

Intensive and long-lasting experience of altered sensory input induces permanent changes in the functional organization of the somatosensory cortex. In addition, an increasing body of evidence suggests the existence of dynamic, short-term and task-dependent adaptation of representational maps within somatosensory cortex. It is hypothesized that somatosensory maps can, not only, be acquired within a short period of time, but might also be set up during periods of training related to specific tasks and subsequently activated dynamically upon performance of that particular task. In order to test this hypothesis we studied the functional organization of somatosensory cortex for a heavily overlearned and frequently performed task for which no new acquisition of a sensory map had to be assumed. To this end, the functional organization of somatosensory cortex for handwriting was compared with the organization during rest in healthy humans. Functional organization of the somatosensory cortex was assessed using non-invasive, neuromagnetic source imaging based on tactile stimulation of the thumb (D1) and little finger (D5) during writing and rest. In different blocks, subjects wrote with their right, dominant and their left hand, respectively. During writing, D1 and D5 of the writing hand were stimulated. To test the reliability of our results all measurements were repeated after 1 week. It was found that amplitudes of somatosensory evoked magnetic fields with latencies of 45 ms were reduced during writing compared with rest. This finding is in accordance with the sensorimotor gating effect. Using source localization we could show that cortical representations of D1 and D5 are more distant during writing with either hand compared with rest. Our data suggest that somatosensory cortical maps undergo rapid modulation depending on task-specific involvement of sensory processing in daily-life overlearned movements. As it is unlikely that a new sensory map is always acquired when a frequently used task such as writing is performed, we suggest that somatosensory cortex switches between different, concurrently pre-existing maps depending on actual requirements. Task-dependent activation of pre-existing maps might be a powerful mechanism to optimize stimulus processing.

Adult↗

PubMed2003

Common neural mechanisms for response selection and perceptual processing.

Behavioral evidence supports a dissociation between response selection (RS; stimulus-to-response [S-R] mapping) and perceptual discrimination (PD): The former may be subject to a central processing bottleneck, whereas the latter is not (Pashler, 1994). We previously (Jiang & Kanwisher, 2003) identified a set of frontal and parietal regions involved in RS as those that produce a stronger signal when subjects follow a difficult S-R mapping rule than an easy mapping rule. Here, we test whether any of these regions are selectively activated by RS and not perceptual processing, as predicted by the central bottleneck view. In Experiment 1, subjects indicated which of four parallel lines was unique in length; PD was indexed by a higher BOLD response when the discrimination was difficult versus easy. Stimuli and responses were closely matched across conditions. We found that all regions-of-interest (ROIs) engaged by RS were also engaged by perceptual processing, arguing against the existence of mechanisms exclusively involved in RS. In Experiments 2 and 3, we asked what processes might go on in these ROIs, such that they could be recruited by both RS and perceptual processing. Our data argue against an account of this common activation in terms of spatial processing or general task difficulty. Thus, PD may recruit the same central processes that are engaged by RS.

Adult↗

PubMed1998

Optimization of phosphorus localization by EFTEM of nucleic acid containing structures.

Energy Filtered Transmission Electron Microscopy (EFTEM) has been used to study nucleic acids localization in unstained thin sections of virus-infected cells. For this purpose, phosphorus maps (P-maps) have been obtained by applying the N-windows Egerton model for background subtraction from data acquired by a non-dedicated TEM Jeol 1200EXII equipped with a post-column PEELS Gatan 666-9000 and a Gatan Image Filter (GIF-100). To prevent possible errors in the evaluation of elemental maps and thus incorrect nucleic acid localization, we have studied different regions of swine testis (ST) cells with similar local density containing either high concentration of nucleic acids (condensed chromatin and ribosomes) or a very low concentration (mitochondria). Special care was taken to optimize the sample preparation conditions to avoid as much as possible the traditional artifacts derived from this source. Selection of the best set of pre-edge images for background fitting was also considered in order to produce "true P-maps". A new software for interactive processing of images series has been applied to estimate this set. Multivariate Statistical Analysis was used as a filtering tool to separate the "useful information" present in the inelastic image series (characteristic signal) from the "non-useful information" (noise and acquisition artifacts). The reconstitution of the original image series preserving mainly the useful information allowed the computation of P-maps with improved signal-to-noise ratio (SNR). This methodology has been applied to study the RNA content of maturation intermediate coronavirus particles found inside infected cells.

Animals↗

PubMed1996

High resolution ultrastructural mapping of total calcium: electron spectroscopic imaging/electron energy loss spectroscopy analysis of a physically/chemically processed nerve-muscle preparation.

We report on a procedure for tissue preparation that combines thoroughly controlled physical and chemical treatments: quick-freezing and freeze-drying followed by fixation with OsO4 vapors and embedding by direct resin infiltration. Specimens of frog cutaneous pectoris muscle thus prepared were analyzed for total calcium using electron spectroscopic imaging/electron energy loss spectroscopy (ESI/EELS) approach. The preservation of the ultrastructure was excellent, with positive K/Na ratios revealed in the fibers by x-ray microanalysis. Clear, high-resolution EELS/ESI calcium signals were recorded from the lumen of terminal cisternae of the sarcoplasmic reticulum but not from longitudinal cisternae, as expected from previous studies carried out with different techniques. In many mitochondria, calcium was below detection whereas in others it was appreciable although at variable level. Within the motor nerve terminals, synaptic vesicles as well as some cisternae of the smooth endoplasmic reticulum yielded positive signals at variance with mitochondria, that were most often below detection. Taken as a whole, the present study reveals the potential of our experimental approach to map with high spatial resolution the total calcium within individual intracellular organelles identified by their established ultrastructure, but only where the element is present at high levels.

Animals↗

PubMed1972

Computerized meiotic mapping in Aspergillus nidulans.

A computer system for the storage and processing of microbial meiotic data has been developed. Based on the language Fortran 4, the program retrieves relevant data and determines the order, map distances, and coefficient of coincidence for any three-gene group. Meiotic data from Aspergillus nidulans were used to test the program. A total of 61 three-gene sequences were processed, and the results were found to be compatible with the published values. The advantages and disadvantages of computer analysis for genetic analysis are discussed.

Aspergillus↗

PubMed1999

Spontaneous recurrence of methampetamine psychosis: increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic change.

We studied the factors precipitating spontaneous recurrences of methamphetamine (MAP)-induced paranoid-hallucinatory states (referred to as "flashbacks") in 28 flashbackers, along with 18 non-flashbackers with a history of MAP psychosis. Plasma levels of catecholamines and their metabolites were assayed in the 28 flashbackers, the 18 non-flashbackers, 8 subjects with persistent MAP psychosis, and 33 normal controls (22 MAP users and 11 non-users). The flashbackers had been exposed to significantly higher numbers of stressful events, and/or MAP-induced frightening paranoid-hallucinatory states during previous MAP use, than the non-flashbackers. Factors triggering the flashbacks met the DSM-III-R criteria for a mild psychosocial stressor. During flashbacks, plasma norepinephrine levels increased and plasma levels of 3-methoxytyramine, which is an indicator of dopamine release, showed a smaller increase. It follows that stressful experiences together with MAP use may induce sensitization to mild psychosocial stressors. Noradrenergic hyperactivity and some degree of increased dopamine release may be involved in this process. Stress sensitization may elicit memories of MAP psychosis associated with stressful experiences in response to mild psychosocial stressors, leading to the occurrence of flashbacks. Sensitization to stress associated with noradrenergic hyperactivity, involving increased dopamine release may be central to spontaneous recurrences of MAP psychosis.

Adaptation, Psychological↗