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At least 145 records · Page 8Linked to original sources

PubMed2006

What makes faces special?

What may be special about faces, compared to non-face objects, is that their neural representation may be fundamentally spatial, e.g., Gabor-like. Subjects matched a sequence of two filtered images, each containing every other combination of spatial frequency and orientation, of faces or non-face 3D blobs, judging whether the person or blob was the same or different. On a match trial, the images were either identical or complementary (containing the remaining spatial frequency and orientation content). Relative to an identical pair of images, a complementary pair of faces, but not blobs, reduced matching accuracy and released fMRI adaptation in the fusiform face area.

Adult↗

PubMed2005

Denatured proteins and early folding intermediates simulated in a reduced conformational space.

Conformations of globular proteins in the denatured state were studied using a high-resolution lattice model of proteins and Monte Carlo dynamics. The model assumes a united-atom and high-coordination lattice representation of the polypeptide conformational space. The force field of the model mimics the short-range protein-like conformational stiffness, hydrophobic interactions of the side chains and the main-chain hydrogen bonds. Two types of approximations for the short-range interactions were compared: simple statistical potentials and knowledge-based protein-specific potentials derived from the sequence-structure compatibility of short fragments of protein chains. Model proteins in the denatured state are relatively compact, although the majority of the sampled conformations are globally different from the native fold. At the same time short protein fragments are mostly native-like. Thus, the denatured state of the model proteins has several features of the molten globule state observed experimentally. Statistical potentials induce native-like conformational propensities in the denatured state, especially for the fragments located in the core of folded proteins. Knowledge-based protein-specific potentials increase only slightly the level of similarity to the native conformations, in spite of their qualitatively higher specificity in the native structures. For a few cases, where fairly accurate experimental data exist, the simulation results are in semiquantitative agreement with the physical picture revealed by the experiments. This shows that the model studied in this work could be used efficiently in computational studies of protein dynamics in the denatured state, and consequently for studies of protein folding pathways, i.e. not only for the modeling of folded structures, as it was shown in previous studies. The results of the present studies also provide a new insight into the explanation of the Levinthal's paradox.

Animals↗

PubMed1998

Weighting hidden Markov models for maximum discrimination.

MOTIVATION: Hidden Markov models can efficiently and automatically build statistical representations of related sequences. Unfortunately, training sets are frequently biased toward one subgroup of sequences, leading to an insufficiently general model. This work evaluates sequence weighting methods based on the maximum-discrimination idea. RESULTS: One good method scales sequence weights by an exponential that ranges between 0.1 for the best scoring sequence and 1.0 for the worst. Experiments with a curated data set show that while training with one or two sequences performed worse than single-sequence Probabilistic Smith-Waterman, training with five or ten sequences reduced errors by 20% and 51%, respectively. This new version of the SAM HMM suite outperforms HMMer (17% reduction over PSW for 10 training sequences), Meta-MEME (28% reduction), and unweighted SAM (31% reduction). AVAILABILITY: A WWW server, as well as information on obtaining the Sequence Alignment and Modeling (SAM) software suite and additional data from this work, can be found at http://www.cse.ucse. edu/research/compbio/sam.html

Algorithms↗

PubMed2001

Comparing protein structures: a Gaussian-based approach to the three-dimensional structural similarity of proteins.

This study describes a new method for comparing three-dimensional protein structures based on an optimal alignment of their steric fields. The method is based upon the use of spherical Gaussian functions located on individual atoms. This representation generates a flexible description of the underlying fold geometry of proteins that can be adjusted by changing the 'width' of the Gaussians. Reducing the width sharpens the representation and leads to a more 'atomlike' description; increasing the width creates a fuzzier representation that preserves the general shape features of the chain fold but with a consequent loss in atomic resolution. The width used in this study is based upon the features of individual atoms and provides a representation that is quite robust with respect to the variety of geometric features typically encountered in the alignment process. In addition, a post-alignment analysis is performed that generates sequence alignments from the corresponding structure alignments. An example, based on five mammalian and fungal matrix metalloproteinase crystal structures (human fibroblast collagenase, neutrophil collagenase, stromelysin, astacin, and adamalysin), illustrates a number of features of the Gaussian-based approach.

Amino Acid Sequence↗

PubMed1995

Characterization, scaling, and partial representation of diffuse and discrete input junctions to CA3 hippocampus.

This paper applies a general mathematical system for characterizing and scaling functional connectivity and information flow across the diffuse (EC) and discrete (DG) input junctions to the CA3 hippocampus. Both gross connectivity and coordinated multiunit informational firing patterns are quantitatively characterized in terms of 32 defining parameters interrelated by 17 equations, and then scaled down according to rules for uniformly proportional scaling and for partial representation. The diffuse EC-CA3 junction is shown to be uniformly scalable with realistic representation of both essential spatiotemporal cooperativity and coordinated firing patterns down to populations of a few hundred neurons. Scaling of the discrete DG-CA3 junction can be effected with a two-step process, which necessarily deviates from uniform proportionality but nonetheless produces a valuable and readily interpretable reduced model, also utilizing a few hundred neurons in the receiving population. Partial representation produces a reduced model of only a portion of the full network where each model neuron corresponds directly to a biological neuron. The mathematical analysis illustrated here shows that although omissions and distortions are inescapable in such an application, satisfactorily complete and accurate models the size of pattern modules are possible. Finally, the mathematical characterization of these junctions generates a theory which sees the DG as a definer of the fine structure of embedded traces in the hippocampus and entire coordinated patterns of sequences of 14-cell links in CA3 as triggered by the firing of sequences of individual neurons in DG.

Animals↗

PubMed1997

Multi-body interactions within the graph of protein structure.

We construct a graphical representation of protein structure based on the 3D C-alpha carbon point set, using the Delaunay tessellation to define interacting quadruples of amino acid residues. The tessellation is filtered by two criteria: interaction distance less than 9.5 angstroms and circumsphere radius less than 8.0 angstroms using dataset of 608 protein structures of low mutual sequence identity and a likelihood ratio test, we show that 3-body and 4-body interactions are indeed significant. We identify particular significant three-body interactions by first reducing the dataset to interacting triples, and classifying amino acid residues in a reduced alphabet. Although cystein was previously shown to be a dominant source of 3-body interactions, we now identify additional significant 3-body interactions of charged, hydrophobic and small residues.

Algorithms↗

PubMed2005

Identification and characterization of regions of the rice genome associated with broad-spectrum, quantitative disease resistance.

Much research has been devoted to understanding the biology of plant-pathogen interactions. The extensive genetic analysis of disease resistance in rice, coupled with the sequenced genome and genomic resources, provides the opportunity to seek convergent evidence implicating specific chromosomal segments and genes in the control of resistance. Published data on quantitative and qualitative disease resistance in rice were synthesized to evaluate the distributions of and associations among resistance loci. Quantitative trait loci (QTL) for resistance to multiple diseases and qualitative resistance loci (R genes) were clustered in the rice genome. R genes and their analogs of the nucleotide binding site-leucine-rich repeat class and genes identified on the basis of differential representation in disease-related EST libraries were significantly associated with QTL. Chromosomal segments associated with broad-spectrum quantitative disease resistance (BS-QDR) were identified. These segments contained numerous positional candidate genes identified on the basis of a range of criteria, and groups of genes belonging to two defense-associated biochemical pathways were found to underlie one BS-QDR region. Genetic dissection of disease QTL confidence intervals is needed to reduce the number of positional candidate genes for further functional analysis. This study provides a framework for future investigations of disease resistance in rice and related crop species.

Blotting, Northern↗

PubMed1991

Global tracking of the ocular fundus pattern imaged by scanning laser ophthalmoscopy.

This paper presents an algorithm for the automatic global tracking of ocular fundus landmarks in video image sequences generated by scanning laser ophthalmoscopy (SLO). The tracking algorithm is based on the computation of the discrete unnormalized cross-correlation of an interactively preselected small template and respective images in time sequences of fundus patterns. The correlation is executed with binary images derived from an automatical threshold limitation of the grey-value images. Due to the [+1/-1] representation of the binary images the unnormalized correlation functions directly relate to the Hamming distance of the template and the objects in the images. Experiments show that even templates with features distorted by noise are accurately recognized at any position. The accuracy of position detection is better than 0.4%. Possible hardware implementations of the algorithm which would reduce computation time are briefly mentioned.

Algorithms↗

PubMed1999

Eye movements and spatial working memory in Parkinson's disease.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

Aged↗

PubMed2001

Sequence-tagged microsatellite profiling (STMP): a rapid technique for developing SSR markers.

We describe a technique, sequence-tagged microsatellite profiling (STMP), to rapidly generate large numbers of simple sequence repeat (SSR) markers from genomic or cDNA. This technique eliminates the need for library screening to identify SSR-containing clones and provides an approximately 25-fold increase in sequencing throughput compared to traditional methods. STMP generates short but characteristic nucleotide sequence tags for fragments that are present within a pool of SSR amplicons. These tags are then ligated together to form concatemers for cloning and sequencing. The analysis of thousands of tags gives rise to a representational profile of the abundance and frequency of SSRs within the DNA pool, from which low copy sequences can be identified. As each tag contains sufficient nucleotide sequence for primer design, their conversion into PCR primers allows the amplification of corresponding full-length fragments from the pool of SSR amplicons. These fragments permit the full characterisation of a SSR locus and provide flanking sequence for the development of a microsatellite marker. Alternatively, sequence tag primers can be used to directly amplify corresponding SSR loci from genomic DNA, thereby reducing the cost of developing a microsatellite marker to the synthesis of just one sequence-specific primer. We demonstrate the utility of STMP by the development of SSR markers in bread wheat.

Australia↗

PubMed1997

Design of a knowledge-based force field for off-lattice simulations of protein structure.

Prediction of protein structure from amino-acid sequence still continues to be an unsolved problem of theoretical molecular biology. One approach to solve it is to construct an appropriate (free) energy function that recognizes the native structures of some selected proteins (whose native structures are known) as the ones distinctively lowest in (free) energy and then to carry out a search of the lowest-energy structure of a new protein. In order to reduce the complexity of the problem and the cost of energy evaluation, the so-called united-residue representation of the polypeptide chain is often applied, in which each amino-acid residue is represented by only a few interaction sites. Once the global energy minimum of the simplified chain has been found, the all-atom structure can easily and reliably be constructed. The search of the lowest-energy structure is usually carried out by means of Monte Carlo methods, though use of more efficient global-optimization methods, especially those of deformation of original energy surface is potentially promising. Monte Carlo search of the conformational space can be accelerated greatly, if the chain is superposed on a discrete lattice (the on-lattice approach). On the other hand, the on-lattice approach prohibits the use of many efficient global-optimization methods, because they require both energy and its space derivatives. The on-lattice methods in which the chain is embedded in the continuous 3D space are, therefore, also worth developing. In this paper we summarize the work on the design and implementation of an off-lattice united-residue force field that is underway in our group, in cooperation with Professor HA. Scheraga of Cornell University, U.S.A.

Models, Molecular↗

PubMed2003

Block structure and stability of the genetic code.

It is known that different codons may be unified into larger groups related to the hierarchical structure, approximate hidden symmetries, and evolutionary origin of the universal genetic code. Using a simplified evolutionary motivated two-letter version of genetic code, the general principles of the most stable coding are discussed. By the complete enumeration in such a reduced code it is strictly proved that the maximum stability with respect to point mutations and shifts in the reading frame needs the fixation of the middle letters within codons in groups with different physico-chemical properties, thus, explaining a key feature of the universal genetic code. The translational stability of the genetic code is studied by the mapping of code onto de Bruijn graph providing both the compact visual representation of mutual relationships between different codons as well as between codons and protein coding DNA sequence and a powerful tool for the investigation of stability of protein coding. Then, the results are extended to four-letter codes. As is shown, the universal genetic code obeys mainly the principles of optimal coding. These results demonstrate the hierarchical character of optimization of universal genetic code with strictly optimal coding being evolved at the earliest stages of molecular evolution. Finally, the universal genetic code is compared with the other natural variants of genetic codes.

Amino Acids↗

PubMed2001

The structure of /s/-sequences: evidence from a disordered system.

This study considers the much-debated markedness and structural status of word-initial /s/-sequences in English by examining the development of KR (male, age 3;6) who has a phonological disorder. Three points in time are discussed: (1) when all initial consonant sequences are reduced to singletons; (2) when only initial /s/-sequences surface correctly; and (3) when all initial consonant sequences surface correctly. While these production patterns are common across developing systems, few accounts have addressed them in terms of structure or markedness. Toward that end, it is argued that KR's /s/-sequences surface as adjuncts, rather than complex onsets. This is explained within optimality theory, whereby high-ranking markedness constraints prevent complex onsets but not adjuncts. The account offers an explanation for consonant sequence asymmetries within and across grammars, allowing for differing representations for /s/-sequences across speakers and for variation exhibited in children's productions. A typology of possible grammars is therefore offered, and clinical implications are considered.

Articulation Disorders↗

PubMed2004

A statistical framework for genomic data fusion.

MOTIVATION: During the past decade, the new focus on genomics has highlighted a particular challenge: to integrate the different views of the genome that are provided by various types of experimental data. RESULTS: This paper describes a computational framework for integrating and drawing inferences from a collection of genome-wide measurements. Each dataset is represented via a kernel function, which defines generalized similarity relationships between pairs of entities, such as genes or proteins. The kernel representation is both flexible and efficient, and can be applied to many different types of data. Furthermore, kernel functions derived from different types of data can be combined in a straightforward fashion. Recent advances in the theory of kernel methods have provided efficient algorithms to perform such combinations in a way that minimizes a statistical loss function. These methods exploit semidefinite programming techniques to reduce the problem of finding optimizing kernel combinations to a convex optimization problem. Computational experiments performed using yeast genome-wide datasets, including amino acid sequences, hydropathy profiles, gene expression data and known protein-protein interactions, demonstrate the utility of this approach. A statistical learning algorithm trained from all of these data to recognize particular classes of proteins--membrane proteins and ribosomal proteins--performs significantly better than the same algorithm trained on any single type of data. AVAILABILITY: Supplementary data at http://noble.gs.washington.edu/proj/sdp-svm

Algorithms↗

PubMed2001

Network formalism for modeling functionally gradient piezoelectric plates and stacks and simulations of RAINBOW ceramic actuators.

A simple network representation is given for a stack of thin, homogeneous piezoelectric plates, executing a single thickness mode of motion. All plates may differ in thickness and material properties, including dielectric loss, ohmic conductivity, and viscous loss. Each plate is driven by a thickness-directed electric field, and all stack elements are connected electrically in series. Functionally gradient single plates and composites are readily modeled by the network, to a desired precision, using a sequence of circuit elements representing stepwise variations in material properties and layer thicknesses. Simulations of RAINBOW (Reduced And Internally Biased Oxide Wafer) ceramics are given.

Journal Article↗

PubMed1993

Cloning the differences between two complex genomes.

The analysis of the differences between two complex genomes holds promise for the discovery of infectious agents and probes useful for genetic studies. A system was developed in which subtractive and kinetic enrichment was used to purify restriction endonuclease fragments present in one population of DNA fragments but not in another. Application of this method to DNA populations of reduced complexity ("representations") resulted in the isolation of probes to viral genomes present as single copies in human DNA, and probes that detect polymorphisms between two individuals. In principle, this system, called representational difference analysis (RDA), may also be used for isolating probes linked to sites of genomic rearrangements, whether occurring spontaneously and resulting in genetic disorders or cancer, or programmed during differentiation and development.

Adenoviridae↗

PubMed1996

Storage of information in transient auditory memory.

This study concerns the manner in which features of auditory stimuli are stored in acoustic memory. Event-related potentials (ERPs) were recorded to sequences of tones in which sequential, infrequent deviant tones were presented in a row, each of which differed from the frequent standard tones along a different stimulus dimension. The object was to determine whether a change in a single feature of a stimulus would have an effect on the entire representation of the standard tone in memory, or only on the representation of the stimulus dimension by which the first deviant differed from the standards. It was found that the amplitude of the mismatch negativity elicited by subsequent deviants was not reduced by the presence of the first deviant, supporting independent storage of features.

Acoustic Stimulation↗

PubMed2001

[Magnetic resonance tomography for planning dental implantation].

PROBLEM: Three-dimensional imaging diagnostics are increasingly recommended before inserting dental implants in high-risk areas and in cases of severe alveolar atrophy. Since patients are exposed to considerable radiation with computed tomography (CT), the possibilities of employing magnetic resonance imaging (MRI) of the jaw as a diagnostic imaging method before inserting dental implants were examined. MATERIAL AND METHOD: Twelve patients and three volunteers were examined by MRI with T1-weighted, fat-suppressed sequences and conventional T1-weighted sequences. The patients wore a diagnostic splint including markers--in the form of capillaries filled with 0.025 x 10(-2) M gadolinium solution (1.5 mm in diameter)--in the planned implant's position and axis. RESULTS: The presentation of relevant anatomic structures and the three-dimensional accuracy of the markers were judged. Metal artefacts were evaluated in vitro. The MRI of the jaw and midface represents the mandibular canal, the maxillary sinus, and other decisive anatomic structures by detailed representation of the connective tissue surrounding the bone. Artefacts of metallic fillings reduce the image quality. CONCLUSION: Obtaining clinical findings and planning before inserting dental implants with the help of MRI can certainly be applied with toothless patients and facilitates three-dimensional planning by representing the exact location and angle of the drill tubes. Local restrictions result from metal extinction artefacts in jaws with teeth and in controls after having inserted titanium implants.

Adolescent↗