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At least 127 records · Page 7Linked to original sources

PubMed2006

A convolutional neural network approach for objective video quality assessment.

This paper describes an application of neural networks in the field of objective measurement method designed to automatically assess the perceived quality of digital videos. This challenging issue aims to emulate human judgment and to replace very complex and time consuming subjective quality assessment. Several metrics have been proposed in literature to tackle this issue. They are based on a general framework that combines different stages, each of them addressing complex problems. The ambition of this paper is not to present a global perfect quality metric but rather to focus on an original way to use neural networks in such a framework in the context of reduced reference (RR) quality metric. Especially, we point out the interest of such a tool for combining features and pooling them in order to compute quality scores. The proposed approach solves some problems inherent to objective metrics that should predict subjective quality score obtained using the single stimulus continuous quality evaluation (SSCQE) method. This latter has been adopted by video quality expert group (VQEG) in its recently finalized reduced referenced and no reference (RRNR-TV) test plan. The originality of such approach compared to previous attempts to use neural networks for quality assessment, relies on the use of a convolutional neural network (CNN) that allows a continuous time scoring of the video. Objective features are extracted on a frame-by-frame basis on both the reference and the distorted sequences; they are derived from a perceptual-based representation and integrated along the temporal axis using a time-delay neural network (TDNN). Experiments conducted on different MPEG-2 videos, with bit rates ranging 2-6 Mb/s, show the effectiveness of the proposed approach to get a plausible model of temporal pooling from the human vision system (HVS) point of view. More specifically, a linear correlation criteria, between objective and subjective scoring, up to 0.92 has been obtained on a set of typical TV videos.

Algorithms↗

PubMed1989

Computer simulations of globular protein folding and tertiary structure.

In summary, although a large number of disparate techniques have been applied to predict the tertiary structure of globular proteins from their amino acid sequence, the solution is not yet at hand. Methodologies for predicting the conformation of constrained, small protein fragments appear to be successful. As the size of the system increases, the level of detail of the treatment decreases; approaches that employ very detailed potentials appear to be limited to about 30-40 residues. Although this is a major advance, methods that reduce the effective number of degrees of freedom are clearly required. Lattice representations coupled to highly efficient Monte Carlo procedures appear to be one such approach. Thus, although a number of theoretical advances in the computer simulation of globular protein structure have been made, much work remains to be done before the globular protein folding problem is solved.

Computer Simulation↗

PubMed2005

Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning.

Movement representations within the human primary motor and somatosensory cortices can be altered by motor learning. Decreases in local GABA concentration and its release may facilitate this plasticity. Here we use in vivo magnetic resonance spectroscopy (MRS) to noninvasively measure serial changes in GABA concentration in humans in a brain region including the primary sensorimotor cortex contralateral to the hand used for an isometric motor sequence learning task. Thirty minutes of motor sequence learning reduced the mean GABA concentration within a 2 x 2 x 2-cm3 voxel by almost 20%. This reduction was specific to motor learning: 30 min of similar, movements with an unlearnable, nonrepetitive sequence were not associated with changes in GABA concentration. No significant changes in GABA concentration were found in the primary sensorimotor cortex ipsilateral to the hand used for learning. These changes suggest remarkably rapid, regionally specific short-term presynaptic modulation of GABAergic input that should facilitate motor learning. Although apparently confined to the contralateral hemisphere, the magnitude of changes seen within a large spectroscopic voxel suggests that these changes occur over a wide local neocortical field.

Adult↗

PubMed2006

Will my protein crystallize? A sequence-based predictor.

We propose a machine-learning approach to sequence-based prediction of protein crystallizability in which we exploit subtle differences between proteins whose structures were solved by X-ray analysis [or by both X-ray and nuclear magnetic resonance (NMR) spectroscopy] and those proteins whose structures were solved by NMR spectroscopy alone. Because the NMR technique is usually applied on relatively small proteins, sequence length distributions of the X-ray and NMR datasets were adjusted to avoid predictions biased by protein size. As feature space for classification, we used frequencies of mono-, di-, and tripeptides represented by the original 20-letter amino acid alphabet as well as by several reduced alphabets in which amino acids were grouped by their physicochemical and structural properties. The classification algorithm was constructed as a two-layered structure in which the output of primary support vector machine classifiers operating on peptide frequencies was combined by a second-level Naive Bayes classifier. Due to the application of metamethods for cost sensitivity, our method is able to handle real datasets with unbalanced class representation. An overall prediction accuracy of 67% [65% on the positive (crystallizable) and 69% on the negative (noncrystallizable) class] was achieved in a 10-fold cross-validation experiment, indicating that the proposed algorithm may be a valuable tool for more efficient target selection in structural genomics. A Web server for protein crystallizability prediction called SECRET is available at http://webclu.bio.wzw.tum.de:8080/secret.

Amino Acid Sequence↗

PubMed1996

Premature disinhibition of P3 generation in schizophrenia.

P300 (P3) is a long-latency cognitive event-related potential (ERP) elicited by relevant target stimuli. P3 was recorded from 11 schizophrenics and 13 normal controls during a cued visual continuous performance task (CPT-AX). Cue-target sequences were presented at short and long interstimulus intervals (ISIs), in order to investigate working memory in schizophrenia. There was no significant between-group difference in P3 amplitude to validly or invalidly cued targets at short ISI. In contrast, P3 amplitude to invalidly cued targets at long ISI was significantly greater in schizophrenics than in controls, suggesting decreased ability to encode or maintain inhibitory representations of stimulus context. P3 amplitude is typically reduced in schizophrenic subjects in the auditory modality, and normal or reduced in the visual modality. This study, which demonstrates a paradoxical P3 increase to targets at long ISI, suggests that P3 impairment in schizophrenia cannot be attributed solely to structural deficits within P3-generator regions.

Adult↗

PubMed2006

Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study.

The Human Proteome Organization (HUPO) recently completed the first large-scale collaborative study to characterize the human serum and plasma proteomes. The study was carried out in different locations and used diverse methods and instruments to compare and integrate tandem mass spectrometry (MS/MS) data on aliquots of pooled serum and plasma from healthy subjects. Liquid chromatography (LC)-MS/MS data sets from 18 laboratories were matched to the International Protein Index database, and an initial integration exercise resulted in 9,504 proteins identified with one or more peptides, and 3,020 proteins identified with two or more peptides. This article uses a rigorous statistical approach to take into account the length of coding regions in genes, and multiple hypothesis-testing techniques. On this basis, we now present a reduced set of 889 proteins identified with a confidence level of at least 95%. We also discuss the importance of such an integrated analysis in providing an accurate representation of a proteome as well as the value such data sets contain for the high-confidence identification of protein matches to novel exons, some of which may be localized in alternatively spliced forms of known plasma proteins and some in previously nonannotated gene sequences.

Blood Proteins↗

PubMed2003

Rats with low exploratory activity in the elevated plus-maze have the increased expression of limbic system-associated membrane protein gene in the periaqueductal grey.

The aim of a present study was to analyse the gene expression profiles in the periaqueductal grey (PAG) of rats related to their exploratory activity in the elevated plus-maze model of anxiety. Animals were divided into the groups according to their exploratory activity in the plus-maze as follows: rats with low activity ('anxious'), moderate activity ('intermediate') and high activity ('non-anxious'). Control animals were not exposed to the elevated plus-maze. The differential expression of genes was analysed using the cDNA representational difference analysis (RDA) in combination with the sequencing and database search. Reverse transcription-polymerase chain reaction with specific primers was applied to confirm the differences found by the RDA. We established that animals displaying the different exploratory activity have also the different gene expression profiles in the PAG. Among the identified genes, we were able to confirm the increased expression of limbic system-associated membrane protein (LSAMP) in animals having the reduced exploratory activity in the elevated plus-maze. 'Anxious' group of rats had 1.6-fold higher expression of LSAMP gene compared to 'non-anxious' animals. By contrast, 'home-cage' control rats and 'intermediate' group did not differ significantly by their LSAMP gene expression level. In conclusion, it is likely that LSAMP plays a role in the regulation of exploratory behaviour of rats in the novel aversive environment.

Animals↗

PubMed1999

Inactivated pbp4 in highly glycopeptide-resistant laboratory mutants of Staphylococcus aureus.

Both vancomycin- and teicoplanin-resistant laboratory mutants of Staphylococcus aureus produce peptidoglycans of altered composition in which the proportion of highly cross-linked muropeptide species is drastically reduced with a parallel increase in the representation of muropeptide monomers and dimers (Sieradzki, K., and Tomasz, A. (1997) J. Bacteriol. 179, 2557-2566; and Sieradzki, K. , and Tomasz, A. (1998) Microb. Drug Resist. 4, 159-168). We now report that the distorted peptidoglycan composition is related to defects in penicillin-binding protein 4 (PBP4); no PBP4 was detectable by the fluorographic assay in membrane preparations from the mutants, and comparison of the sequence of pbp4 amplified from the mutants indicated disruption of the gene by two types of abnormalities, a 17-amino acid long duplication starting at position 305 of the pbp4 gene was detected in the vancomycin-resistant mutant, and a stop codon was found to be introduced into the pbp4 KTG motif at position 261 in the mutant selected for teicoplanin resistance. Additional common patterns of disturbances in the peptidoglycan metabolism of the mutants are indicated by the increased sensitivity of mutant cell walls to the M1 muramidase and decreased sensitivity to lysostaphin, which is a reversal of the susceptibility pattern of the parental cell walls. Furthermore, the results of high performance liquid chromatography analysis of lysostaphin digests of peptidoglycan suggest an increase in the average chain length of the glycan strands in the peptidoglycan of the glycopeptide-resistant mutants. The increased molar proportion of muropeptide monomers in the cell wall of the glycopeptide-resistant mutants should provide binding sites for the "capture" of vancomycin and teicoplanin molecules, which may be part of the mechanism of glycopeptide resistance in S. aureus.

Amino Acid Sequence↗

PubMed2001

NPAS2: an analog of clock operative in the mammalian forebrain.

Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.

ARNTL Transcription Factors↗

PubMed2003

Protein fragment reconstruction using various modeling techniques.

Recently developed reduced models of proteins with knowledge-based force fields have been applied to a specific case of comparative modeling. From twenty high resolution protein structures of various structural classes, significant fragments of their chains have been removed and treated as unknown. The remaining portions of the structures were treated as fixed - i.e., as templates with an exact alignment. Then, the missed fragments were reconstructed using several modeling tools. These included three reduced types of protein models: the lattice SICHO (Side Chain Only) model, the lattice CABS (Calpha + Cbeta + Side group) model and an off-lattice model similar to the CABS model and called REFINER. The obtained reduced models were compared with more standard comparative modeling tools such as MODELLER and the SWISS-MODEL server. The reduced model results are qualitatively better for the higher resolution lattice models, clearly suggesting that these are now mature, competitive and complementary (in the range of sparse alignments) to the classical tools of comparative modeling. Comparison between the various reduced models strongly suggests that the essential ingredient for the sucessful and accurate modeling of protein structures is not the representation of conformational space (lattice, off-lattice, all-atom) but, rather, the specificity of the force fields used and, perhaps, the sampling techniques employed. These conclusions are encouraging for the future application of the fast reduced models in comparative modeling on a genomic scale.

Amino Acid Sequence↗

PubMed2005

Genetically engineered vaccines.

The application of recombinant DNA technology to allergen research has provided the sequence information and genetic material to produce new types of allergy vaccines. One general strategy has been to use the knowledge to produce synthetic peptides that represent selected T-cell or B-cell epitopes. The production of genetically engineered allergens provides an alternative strategy to construct hypoallergenic vaccines, which can provide a better and less selected representation of the epitopes. Many strategies have been used to produce such hypoallergens, and their ability to reduce allergenicity has been amply demonstrated by skin and nasal provocation tests. The retention of T cell-stimulating activity has also been demonstrated, and a consistent feature of the vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity, the ability to induce anti-allergen IgG antibody. The lead hypoallergens have been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1. A clinical trial with these medicaments has shown the ability to modify IgE and IgG antibody production, skin test reactivity, and symptom scores. This is the first trial of a recombinant allergy vaccine, and it has set a benchmark for further studies. A new generation of hypoallergens is now being produced based on the detailed knowledge of the tertiary structures of the allergens and of the T-cell and B-cell epitopes. The modifications have been made to change the topography of the allergens while retaining a stable, folding structure. In the case of Bet v 1, tertiary structures of hypoallergens have been determined. Structurally modeled hypoallergens have been produced for pollen, venom, food, and latex allergens, with promising characteristics from preclinical studies.

Allergens↗

PubMed2003

Processing emotional tone from speech in Parkinson's disease: a role for the basal ganglia.

In this study, individuals with Parkinson's disease were tested as a model for basal ganglia dysfunction to infer how these structures contribute to the processing of emotional speech tone (emotional prosody). Nondemented individuals with and without Parkinson's disease (n = 21/group) completed neuropsychological tests and tasks that required them to process the meaning of emotional prosody in various ways (discrimination, identification, emotional feature rating). Individuals with basal ganglia disease exhibited abnormally reduced sensitivity to the emotional significance of prosody in a range of contexts, a deficit that could not be attributed to changes in mood, emotional-symbolic processing, or estimated frontal lobe cognitive resource limitations in most conditions. On the basis of these and broader findings in the literature, it is argued that the basal ganglia provide a critical mechanism for reinforcing the behavioral significance of prosodic patterns and other temporal representations derived from cue sequences (Lieberman, 2000), facilitating cortical elaboration of these events.

Affect↗

PubMed2003

Identification of regulatory binding sites using minimum spanning trees.

Recognition of protein-binding sites from the upstream regions of genes is a highly important and unsolved problem. In this paper, we present a new approach for studying this challenging issue. We formulate the binding-site recognition problem as a cluster identification problem, i.e., to identify clusters in a data set that exhibit significantly different features (e.g., density) than the overall background of the data set. We have developed a general framework for solving such a cluster identification problem. The foundation of the framework is a rigorous relationship between data clusters and subtrees of a minimum spanning tree (MST) representation of a data set. We have proposed a formal and general definition of clusters, and have demonstrated that a cluster is always represented as a connected component of the MST, and further it corresponds to a substring of a linear representation of the MST. Hence a cluster identification problem is reduced to a problem of finding substrings with certain features, for which algorithms have been developed. We have applied this MST-based cluster identification algorithm to a number of binding site identification problems. The results are highly encouraging.

Algorithms↗

PubMed1999

Gene therapy of genetic diseases and cancer.

The scope of gene transfer applications in human therapy has expanded enormously over the last 15 years to include not only several types of genetic diseases but also a variety of genetic approaches to the treatment of cancer. Hematopoietic stem cells have been considered excellent targets for therapeutic gene transfer because of their capacity for self-renewal and for differentiation into multiple cellular lineages. Retrovirus-mediated gene transfer has been tested for treatment of diseases that specifically affect the hematopoietic system, such as adenosine deaminase deficiency and chronic granulomatous disease. Storage disorders such as Gaucher disease, Hurler syndrome and Hunter syndrome, genetic deficiencies that affect a broad range of tissue types, may also be amenable to treatment by gene transfer into hematopoietic cells, owing to the release of enzyme expressed in transduced cells with subsequent uptake by untransduced cells ("metabolic cross-correction"). Hematopoietic stem cells may also be targeted for introduction of drug-resistance genes for the purpose of protecting normal tissues from the toxic side-effects of cancer chemotherapeutic agents, thus allowing more effective antitumor chemotherapy. The danger of introducing drug-resistance function into tumor cells may be dealt with by including sequences specifically designed to reduce expression of oncogenes or to restore expression of tumor suppressor genes. Current limitations on the efficiency of gene transfer into hematopoietic stem cells may be alleviated by the development of new vector systems such as adeno-associated virus or lentivirus vectors, or by advances in cell processing that render hematopoietic cells more susceptible to transduction. Drug-resistance genes may also be applied for in vivo selection to expand the representation of a small proportion of transduced hematopoietic cells. These approaches toward increasing the frequency of hematopoietic cell transduction contribute to the anticipated feasibility of gene therapy for genetic diseases and cancer.

Child↗

PubMed2026

Equity in genome sequencing for rare disease diagnosis: a cross-sectional analysis of data from the UK 100,000 Genomes Project.

BACKGROUND: Genome sequencing has improved rare disease diagnosis and is now part of routine clinical care in the National Health Service in England. Automated prioritisation pipelines narrow millions of variants per patient to a small subset for clinical review, a process that relies on allele frequency resources that do not fully represent human genetic diversity. We assessed ancestry-related differences in variant prioritisation and diagnostic outcomes in patients from the UK 100,000 Genomes Project. METHODS: We analysed 29,405 rare disease probands with genome sequencing and linked clinical outcomes data. We used multivariable regression to assess ancestry-related differences in the number of variants prioritised for clinical review, the proportion of prioritised variants that were recorded as diagnostic, and diagnostic yield. We also evaluated the use of ancestry-stratified allele frequency filters derived from an independent, diverse UK cohort (n = 33,724). FINDINGS: Compared with the European ancestry group, the East African group had nearly three times more variants prioritised for clinical review (IRR 2.77, 95% CI 2.33-3.29). Other non-European groups also had significantly higher counts. Diagnostic yield was similar across ancestry groups after adjustment (LRT p = 0.1650). Prioritised variants were less likely to be recorded as diagnostic in East African (OR 0.32, 95% CI 0.22-0.46), West African (0.47, 0.39-0.57), South Asian (0.65, 0.58-0.73), and Middle Eastern (0.68, 0.54-0.86) groups. Applying ancestry-stratified allele-frequency filters removed 3.1% of prioritised variants overall-24.3% in the East African group-without loss of diagnostic sensitivity, including 29.5% of recorded VUS in this group. INTERPRETATION: Differences in the likelihood of prioritised variants being recorded as diagnostic partly reflect limitations of current allele frequency resources, which use broad population groupings that mask within-group diversity. Increased representation of diverse ancestries in reference databases and better estimation of ancestry-appropriate allele frequencies will help reduce inefficiencies and improve equity in variant prioritisation for rare disease diagnosis. FUNDING: The UK Department of Health and Social Care and the EU's Horizon 2020 Research and Innovation Programme.

Humans↗

PubMed1992

Ciliary beating in three dimensions: steps of a quantitative description.

We document a novel approach for quantitative assessment of ciliary activity, exemplified in rapid three-dimensional cyclic motion of the frontal cirri of Stylonychia. Cells held under voltage-clamp control are stimulated by step pulses to elicit reproducible hyperpolarization- or depolarization-induced ciliary motor responses. High-speed video recording at 200 fields per second is used for imaging ciliary organelles of the same cell in two perspectives: the axial view and, following cell rotation by 90 degrees, the lateral view. From video sequences of typically 1 s, the contours of the cirral images are determined and digitized. Computer programs are established to (1) reduce an observed image to a "ciliary axis", (2) sort series of axes by template to generate an averaged ciliary cycle in 2D-projection, and (3) to associate the generalized axial and lateral 2D-images for generation of a sequence of three-dimensional images, which quantitatively represent the cycle in space and time. The method allows us to produce predetermined perspectives of images selected from the ciliary cycle, and to generate stereo views for graphical representation of ciliary motion. The approach includes a potential for extraction of the complete microtubular sliding program of a cilium under reproducible electric stimulation of the ciliary membrane.

Animals↗

PubMed1991

Molecular modeling of the multidomain structures of the proteoglycan binding region and the link protein of cartilage by neutron and synchrotron X-ray scattering.

The interaction of proteoglycan monomers with hyaluronate in cartilage is mediated by a globular binding region at the N-terminus of the proteoglycan monomer; this interaction is stabilized by link protein. Sequences show that both the binding region (27% carbohydrate) and the link protein (6% carbohydrate) contain an immunoglobulin (Ig) fold domain and two proteoglycan tandem repeat (PTR) domains. Both proteins were investigated by neutron and synchrotron X-ray solution scattering, in which nonspecific aggregate formation was reduced by the use of citraconylation to modify surface lysine residues. The neutron and X-ray radius of gyration RG of native and citraconylated binding region is 5.1 nm, and the cross-sectional RG (RXS) is 1.9-2.0 nm. No neutron contrast dependence of the RG values was observed; however, a large contrast dependence was seen for the RXS values which is attributed to the high carbohydrate content of the binding region. The neutron RG for citraconylated link protein is 2.9 nm, its RXS is 0.8 nm, and these data are also independent of the neutron contrast. The scattering curves of binding region and link protein were modeled using small spheres. Both protein structures were defined initially by the representation of one domain by a crystal structure for a variable Ig fold and a fixed volume for the two PTR domains calculated from sequence data. The final models showed that the different dimensions and neutron contrast properties of binding region compared to link protein could be attributed to an extended glycosylated C-terminal peptide with extended carbohydrate structures in the binding region.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Limiting detection of an amplification signal for HLA-D region and VNTR genes by 32P-PCR.

The limiting detection signal for identification of human genetic markers, such as HLA-D and VNTR genes, was determined using DNA isolated from a series of decreasing numbers of lymphocytes carrying the target marker in the polymerase chain reaction (PCR). The PCR procedure was assembled by incorporating 32P-labeled dCTP in the reaction mixture. Primers specific for detection of MHC Class II genes such as HLA-DR1, -DR2, -DRw52 and -DRw53 were utilized when cells were mismatched by one DR type, and primers for the identification of the region of variable number of tandem repeats (VNTRs) were utilized where cells had the same DR types. The 32P-incorporated amplified DNA was analyzed by polyacrylamide gel electrophoresis followed by exposure to x-ray film. The sensitivity of the test varied for different allelic markers as evaluated by amplification of DNA from each set of a mixture of lymphocytes. The target HLA-DR markers were detectable in a cell ratio of as high as 1:100,000, whereas the VNTR markers were detectable at a 1:1000 cell ratio. The approach described here offers certain advantages: 1) increased sensitivity, 2) quantitative power, 3) reduced assay time, 4) simplified procedure and 5) less expense. This method provides valuable information for studies involving forensic specimens and marrow engraftment after allogenic bone marrow transplantation (BMT) that require discrete representation of one allele relative to another in a heterozygous sample where limited quantities of target DNA are available.

Base Sequence↗