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At least 523 records · Page 29Linked to original sources
PubMed2006

A pulse sequence for rapid in vivo spin-locked MRI.

PURPOSE: To develop a novel pulse sequence called spin-locked echo planar imaging (EPI), or (SLEPI), to perform rapid T1rho-weighted MRI. MATERIALS AND METHODS: SLEPI images were used to calculate T1rho maps in two healthy volunteers imaged on a 1.5-T Sonata Siemens MRI scanner. The head and extremity coils were used for imaging the brain and blood in the popliteal artery, respectively. RESULTS: SLEPI-measured T1rho was 83 msec and 103 msec in white (WM) and gray matter (GM), respectively, 584 msec in cerebrospinal fluid (CSF), and was similar to values obtained with the less time-efficient sequence based on a turbo spin-echo readout. T1rho was 183 msec in arterial blood at a spin-lock (SL) amplitude of 500 Hz. CONCLUSION: We demonstrate the feasibility of the SLEPI pulse sequence to perform rapid T1rho MRI. The sequence produced images of higher quality than a gradient-echo EPI sequence for the same contrast evolution times. We also discuss applications and limitations of the pulse sequence.

Brain Mapping↗
PubMed1994

Chromatin self-organization by mutation bias.

Proteins, on binding to a DNA sequence, alter the frequency and quality of mutations that occur in the sequence. This represents a reverse flow of information from proteins to DNA. Nucleosome binding causes patterns of UV-induced damage which, when converted to mutations by replication, will phase nucleosomes. We propose that DNA binding proteins create their own high- or low-affinity binding sites along DNA sequences by biased mutational pressure.

Biological Evolution↗
PubMed2005

Computational approach involving use of the internal transcribed spacer 1 region for identification of Mycobacterium species.

The rapid and reliable identification of clinically significant Mycobacterium species is a challenge for diagnostic laboratories. This study evaluates a unique sequence-dependent identification algorithm called MycoAlign for the differential identification of Mycobacterium species. The MycoAlign system uses pan-Mycobacterium-specific primer amplification in combination with a customized database and algorithm. The results of testing were compared with conventional phenotypic assays and GenBank sequence comparisons using the 16S rRNA target. Discrepant results were retested and evaluated using a third independent database. The custom database was generated using the hypervariable sequences of the internal transcribed spacer 1 (ITS-1) region of the rRNA gene complex from characterized Mycobacterium species. An automated sequence-validation process was used to control quality and specificity of evaluated sequence. A total of 181 Mycobacterium strains (22 reference strains and 159 phenotypically identified clinical isolates) and seven nonmycobacterial clinical isolates were evaluated in a comparative study to validate the accuracy of the MycoAlign algorithm. MycoAlign correctly identified all referenced strains and matched species in 94% of the phenotypically identified Mycobacterium clinical isolates. The ITS-1 sequence target showed a higher degree of specificity in terms of Mycobacterium identification than the 16S rRNA sequence by use of GenBank BLAST. This study showed the MycoAlign algorithm to be a reliable and rapid approach for the identification of Mycobacterium species and confirmed the superiority of the ITS-1 region sequence over the 16S rRNA gene sequence as a target for sequence-based species identification.

Base Sequence↗
PubMed1999

Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report.

OBJECTIVES: Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy (1H-MRS) after birth asphyxia. MATERIALS AND METHODS: Thirty newborn infants suspected of having perinatal asphyxia (Apgar score < 3) were studied. The mean gestational age was 37 weeks, mean age at the MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for imaging and spectroscopy. None of the babies had mechanically assisted ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were obtained. 1H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. RESULTS: Image quality was good in 25 of 30 babies. 1H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. CONCLUSIONS: This study suggests that 1H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites.

Aspartic Acid↗
PubMed1996

Toward the development of a gene index to the human genome: an assessment of the nature of high-throughput EST sequence data.

A rigorous analysis of the Merck-sponsored EST data with respect to known gene sequences increases the utility of the data set and helps refine methods for building a gene index. A highly curated human transcript data base was used as a reference data set of known genes. A detailed analysis of EST sequences derived from known genes was performed to assess the accuracy of EST sequence annotation. The EST data was screened to remove low-quality and low-complexity sequences. A set of high-quality ESTs similar to the transcript data base was identified using BLAST; this subset of ESTs was compared with the set of known genes using the Smith-Waterman algorithm. Error rates of several types were assessed based on a flexible match criterion defining sequence identity. The rate of lane-tracking errors is very low, approximately 0.5%. Insert size data is accurate within approximately 20%. Reversed clone and internal priming error rates are approximately 5% and 2.5%, respectively, contributing to the incorrect identification of reads as 3' ends of genes. Follow-up investigation reveals that a significant number of clones, miscategorized as reversed, represent overlapping genes on the opposite strand of entries in the transcript data base. Relevance of these results to the creation of a high-quality index to the human genome capable of supporting diverse genomic investigations is discussed.

Algorithms↗
PubMed1997

Functional diversity of PH domains: an exhaustive modelling study.

BACKGROUND: Pleckstrin homology (PH) domains are found in many proteins involved in signal transduction or cytoskeletal organization. The general function for the domain is still unclear; phospholipid binding of some PH domains and a strong electrostatic polarization in the experimental structures suggest a role in localization on membranes. We have analyzed the electrostatic properties and the spatial amino acid distribution from homology models of the entire PH domain family. RESULTS: Despite the sequence divergence, the quality of the models is sufficient for our study. Most PH domains have an electrostatic polarization similar to the experimental structures. but roughly half of the PH domains linked to a Dbl homology domain have very different electrostatic properties. We also found a striking electrostatic complementarity in some internal PH domain repeats. The analysis of the spatial distribution of amino acids identified residues in the phospholipid-binding site of the spectrin and dynamin PH domains as specific for these domains. CONCLUSIONS: The mostly conserved electrostatic polarization supports a general function in binding to phospholipid membranes. But the presence of PH domains with opposite polarity suggests that ligands and functions have diverged during evolution. We also demonstrate homology modelling as a general sequence analysis tool that can yield significantly more information than conventional analysis.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2001

Homology modelling of the human eukaryotic initiation factor 5A (eIF-5A).

Homology modelling of the human eIF-5A protein has been performed by using a multiple predictions strategy. As the sequence identity between the target and the template proteins is nearly 30%, which is lower than the commonly used threshold to apply with confidence the homology modelling method, we developed a specific predictive scheme by combining different sequence analyses and predictions, as well as model validation by comparison to structural experimental information. The target sequence has been used to find homologues within sequence databases and a multiple alignment has been created. Secondary structure for each single protein has been predicted and compared on the basis of the multiple sequence alignment, in order to evaluate and adjust carefully any gap. Therefore, comparative modelling has been applied to create the model of the protein on the basis of the optimized sequence alignment. The quality of the model has been checked by computational methods and the structural features have been compared to experimental information, giving us a good validation of the reliability of the model and its correspondence to the protein structure in solution. Last, the model was deposited in the Protein Data Bank to be accessible for studies on the structure-function relationships of the human eIF-5A.

Amino Acid Sequence↗
PubMed2003

Ultrafast multiplanar determination of left ventricular hypertrophy in spontaneously hypertensive rats with single-shot spin-echo nuclear magnetic resonance imaging.

OBJECTIVE: To determine whether left ventricular hypertrophy can be correctly evaluated in hypertensive rats with a new nuclear magnetic resonance (NMR) imaging modality that is relatively simple to operate and provides results of constant quality while offering a high signal-to-noise ratio. DESIGN Left ventricular mass as calculated from the NMR imaging analysis was compared with the actual left ventricular mass measured by gravimetry. METHODS: Single-shot ultrafast spin-echo (SSFSE) imaging of hearts of Wistar-Kyoto rats and spontaneously hypertensive rats was performed at 4 T. Left ventricular mass was determined by using Simpson's rule on stacks of images acquired in systole and diastole. RESULTS: SSFSE NMR imaging performed in systole or in diastole evaluated and quantified left ventricular hypertrophy in hearts of spontaneously hypertensive rats very similarly to gravimetry. The left ventricular mass as determined by NMR was in good accordance with the actual left ventricular weight (SEE: 30.39 and 35.86 mg for the systolic and diastolic NMR acquisitions, respectively). CONCLUSION: Using an SSFSE sequence, high-quality NMR images of the rat heart can be generated very reliably with sufficient contrast and temporal and spatial resolution, and allow precise, non-invasive and fast characterization of left ventricular hypertrophy in a hypertensive rat model.

Animals↗
PubMed1994

Solid-phase syntheses of phosphorylated and thiophosphorylated peptides related to an EGFR sequence.

The 13 amino acid EGFR-sequence AENAEYLRVAPQS-NH2 containing the in vivo autophosphorylated Tyr 1171, was synthesized by Fmoc continuous-flow SPPS with and without N-terminal Boc protection. In addition to the native sequence, peptides in which tyrosine was exchanged by serine and threonine were prepared. Global phosphorylation of the unprotected hydroxyl amino acids on the resin with di-tert-butyl-N,N-diethylphosphoramidite and 1H-tetrazole followed by in situ oxidation of the resulting phosphites with tert-butyl hydroperoxide or with dibenzoyl tetrasulfide resulted in the tyrosine-, serine- and threonine-phosphorylated and -thiophosphorylated sequences, respectively. The quality of the products after phosphorylation with N-terminal protection was better than without. Whereas the serine- and threonine-thiophosphate group was stable, tyrosine-thiophosphate turned out to be hydrolytically labile under acidic conditions. The rate of hydrolysis was determined with the tyrosine-thiophosphorylated model dipeptide Ac-Tyr-Gly-OH between pH 0.1 and 8. Hydrolysis was fastest at pH 3, with a half-time of 12.5 h at room temperature. The tyrosine-thiophosphate group was completely stable at pH 8.

Amino Acid Sequence↗
PubMed2003

APDB: a novel measure for benchmarking sequence alignment methods without reference alignments.

MOTIVATION: We describe APDB, a novel measure for evaluating the quality of a protein sequence alignment, given two or more PDB structures. This evaluation does not require a reference alignment or a structure superposition. APDB is designed to efficiently and objectively benchmark multiple sequence alignment methods. RESULTS: Using existing collections of reference multiple sequence alignments and existing alignment methods, we show that APDB gives results that are consistent with those obtained using conventional evaluations. We also show that APDB is suitable for evaluating sequence alignments that are structurally equivalent. We conclude that APDB provides an alternative to more conventional methods used for benchmarking sequence alignment packages.

Algorithms↗
PubMed2004

Quantitative image quality evaluation of pixel-binning in a flat-panel detector for x-ray fluoroscopy.

X-ray fluoroscopy places stringent design requirements on new flat-panel (FP) detectors, requiring both low-noise electronics and high data transfer rates. Pixel-binning, wherein data from more that one detector pixel are collected simultaneously, not only lowers the data transfer rate but also increases x-ray counts and pixel signal-to-noise ratio (SNR). In this study, we quantitatively assessed image quality of image sequences from four acquisition methods; no-binning and three types of binning; in synthetic images using a clinically relevant task of detecting an extended guidewire in a four-alternative forced-choice paradigm. Binning methods were conventional data-line (D) and gate-line (G) binning, and a novel method in which alternate frames in an image sequence used D and G binning. Two detector orientations placed the data lines either parallel or perpendicular to the guide wire. At a low exposure of 0.6 microR (1.548 x 10(-10) C/kg) per frame, irrespective of detector orientation, D binning with its reduced electronic noise was significantly (p<0.1) better than the other acquisition methods. On average, alternate binning performed better than G binning. At a higher exposure of 4.0 microR (10.32 x 10(-10) C/kg) per frame, with data lines parallel to the guidewire, detection with D binning was significantly (p<0.1) better than G binning. However, with data lines perpendicular to the guidewire, G binning was significantly (p<0.1) better than D binning because the partial area effect was reduced. Alternate binning was the best binning method when results were averaged over both orientations, and it was as good as the best binning method at either orientation. In addition, at low and high exposures, alternate binning gave a temporally fused image with a smooth guidewire, an important image quality feature not assessed in a detection experiment. While at high exposure, detection with no binning was as good, or better, than the best binning method, it might be impractical at fluoroscopy imaging rates. A computational observer model based on signal detection theory successfully fit data and was used to predict effects of similar acquisition methods. Results from this study suggest the use of exposure-dependent detector binning in fluoroscopy that switches between D binning and alternate binning at low and high exposures, respectively.

Fluoroscopy↗
PubMed2003

Fast and sensitive multiple alignment of large genomic sequences.

BACKGROUND: Genomic sequence alignment is a powerful method for genome analysis and annotation, as alignments are routinely used to identify functional sites such as genes or regulatory elements. With a growing number of partially or completely sequenced genomes, multiple alignment is playing an increasingly important role in these studies. In recent years, various tools for pair-wise and multiple genomic alignment have been proposed. Some of them are extremely fast, but often efficiency is achieved at the expense of sensitivity. One way of combining speed and sensitivity is to use an anchored-alignment approach. In a first step, a fast search program identifies a chain of strong local sequence similarities. In a second step, regions between these anchor points are aligned using a slower but more accurate method. RESULTS: Herein, we present CHAOS, a novel algorithm for rapid identification of chains of local pair-wise sequence similarities. Local alignments calculated by CHAOS are used as anchor points to improve the running time of DIALIGN, a slow but sensitive multiple-alignment tool. We show that this way, the running time of DIALIGN can be reduced by more than 95% for BAC-sized and longer sequences, without affecting the quality of the resulting alignments. We apply our approach to a set of five genomic sequences around the stem-cell-leukemia (SCL) gene and demonstrate that exons and small regulatory elements can be identified by our multiple-alignment procedure. CONCLUSION: We conclude that the novel CHAOS local alignment tool is an effective way to significantly speed up global alignment tools such as DIALIGN without reducing the alignment quality. We likewise demonstrate that the DIALIGN/CHAOS combination is able to accurately align short regulatory sequences in distant orthologues.

Algorithms↗
PubMed2006

Improved repeat identification and masking in Dipterans.

Repetitive sequences are a major constituent of many eukaryote genomes and play roles in gene regulation, chromosome inheritance, nuclear architecture, and genome stability. The identification of repetitive elements has traditionally relied on in-depth, manual curation and computational determination of close relatives based on DNA identity. However, the rapid divergence of repetitive sequence has made identification of repeats by DNA identity difficult even in closely related species. Hence, the presence of unidentified repeats in genome sequences affects the quality of gene annotations and annotation-dependent analyses (e.g. microarray analyses). We have developed an enhanced repeat identification pipeline using two approaches. First, the de novo repeat finding program PILER-DF was used to identify interspersed repetitive elements in several recently finished Dipteran genomes. Repeats were classified, when possible, according to their similarity to known elements described in Repbase and GenBank, and also screened against annotated genes as one means of eliminating false positives. Second, we used a new program called RepeatRunner, which integrates results from both RepeatMasker nucleotide searches and protein searches using BLASTX. Using RepeatRunner with PILER-DF predictions, we masked repeats in thirteen Dipteran genomes and conclude that combining PILER-DF and RepeatRunner greatly enhances repeat identification in both well-characterized and un-annotated genomes.

Animals↗
PubMed2000

A comparison between segmented k-space FLASH and interleaved spiral MR coronary angiography sequences.

A direct comparison of segmented fast low-angle short (FLASH) imaging and interleaved spiral magnetic resonance coronary angiography (MRCA) during free respiration using navigator echo has been performed. MRCA images were acquired in 30 normal subjects and 15 patients with coronary artery disease (CAD). Images of the right coronary artery were acquired during free respiration using navigator echo gating for both a segmented k-space FLASH sequence (8 views/segment, segment duration 105 msec) and an interleaved spiral sequence (20 interleaves, spiral read-out period 19 msec). Image quality was scored by three independent blinded observers, and coronary artery signal-to-noise ratio (SNR) and coronary artery/epicardial fat contrast-to-noise ratio (CNR) were measured. There was a significant improvement in image quality when coronary images were acquired with the interleaved spiral sequence (spiral 2. 3 vs. FLASH 1.8; P = 0.002). This was associated with an increase in the coronary artery SNR (16.6 +/- 6.9 vs. 11.8 +/- 5.0; P < 0.001), the coronary artery/epicardial fat CNR (12.5 +/- 6.1 vs. 7.4 +/- 4.0, P < 0.001), and the image resolution (256 x 256 vs. 256 x 128). However, there was a 12% increase in acquisition time for the interleaved spiral sequence. Image quality, SNR, CNR, and resolution can be improved using an interleaved spiral sequence. These improvements are secondary to the intrinsic characteristics of spiral imaging and the short acquisition period, which reduces the effects of both cardiac and respiratory motion.

Adult↗
PubMed1995

Renal arteries: evaluation with optimized 2D and 3D time-of-flight MR angiography.

PURPOSE: To compare two-dimensional (2D) and three-dimensional (3D) time-of-flight (TOF) techniques in magnetic resonance (MR) angiography of renal arteries. MATERIALS AND METHODS: In 46 patients, MR angiography was performed with 3D tilted optimized non-saturating excitation (TONE), 3D fast imaging with steady precession (FISP), and 2D fast low-angle shot (FLASH) during breath holding. Intraarterial angiography was used as a reference. MR angiograms were evaluated for stenoses, length of renal arteries, accessory arteries, venous overlap, and image quality. RESULTS: The 3D TONE sequence was best for detection of severe stenoses (sensitivity, 100%; specificity, 89%), delineation of accessory arteries, and image quality. Overlap of renal veins was the most important disadvantage of 2D FLASH. Decreased saturation effects, however, can be advantageous in 2D TOF imaging. CONCLUSION: Use of the 3D TONE sequence provided improved image quality and diagnostic value compared with 3D FISP technique. The 2D TOF sequence can be useful in combination with the 3D TONE sequence.

Adult↗
PubMed2004

Towards quality control for DNA microarrays.

We present a framework for detecting probes in oligonucleotide microarrays that may add significant error to measurements in hybridization experiments. Four types of so-called degenerate probe behavior are considered: secondary structure formation, self-dimerization, cross-hybridization, and dimerization. The framework uses a well-established model for computing the free energy of nucleic acid sequence hybridization and a novel method for the detection of patterns in hybridization experiment data. Our primary result is the identification of unique patterns in hybridization experiment data that are shown to correlate with each type of degenerate probe behavior. A support function for identifying degenerate probes from a large set of hybridization experiments is given and some preliminary experimental results are given for the Affymetrix HuGeneFL GeneChip. Finally, we show a strong relationship between the Affymetrix discrimination measure for a probe and the free-energy estimate from theoretical models of hybridization. In particular, probes on the HuGeneFL GeneChip with high free-energy estimates (weak hybridization) have almost always approximately zero discrimination. The framework can be applied to any Affymetrix oligonucleotide array, and the software is made freely available to the community.

Base Sequence↗
PubMed2003

PipeAlign: A new toolkit for protein family analysis.

PipeAlign is a protein family analysis tool integrating a five step process ranging from the search for sequence homologues in protein and 3D structure databases to the definition of the hierarchical relationships within and between subfamilies. The complete, automatic pipeline takes a single sequence or a set of sequences as input and constructs a high-quality, validated MACS (multiple alignment of complete sequences) in which sequences are clustered into potential functional subgroups. For the more experienced user, the PipeAlign server also provides numerous options to run only a part of the analysis, with the possibility to modify the default parameters of each software module. For example, the user can choose to enter an existing multiple sequence alignment for refinement, validation and subsequent clustering of the sequences. The aim is to provide an interactive workbench for the validation, integration and presentation of a protein family, not only at the sequence level, but also at the structural and functional levels. PipeAlign is available at http://igbmc.u-strasbg.fr/PipeAlign/.

Internet↗
PubMed1995

Schizoaffective psychoses: genetical clues to classification.

The diagnostic classification of schizoaffective psychoses has varied much since Kasanin introduced the concept in 1933. The various classifications have agreed that schizoaffective psychoses present a combination of schizophreniform and affective symptoms, but the diagnostic criteria differ as to the number, quality, and time sequence of the symptoms even in recent classifications like RDC, DSM-III-R, and ICD-10. The classifications are syndromatical, and the etiology of the schizoaffective psychoses is still undetermined apart from evidence for a strong genetic factor. Results from family, twin, and adoption studies are divergent, but all the same, support a separate classification of broadly defined schizoaffective psychoses as possibly being phenotypical variations or expressions of genetic interforms between schizophrenia and affective psychoses.

Bipolar Disorder↗