On John Allen's critique of induction.
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Computational Biology↗
Biomedical subjects
L A Kelley
Publications and source records attributed to L A Kelley.
Enhanced genome annotation using structural profiles in the program 3D-PSSM.
A method (three-dimensional position-specific scoring matrix, 3D-PSSM) to recognise remote protein sequence homologues is described. The method combines the power of multiple sequence profiles with knowledge of protein structure to provide enhanced recognition and thus functional assignment of newly sequenced genomes. The method uses structural alignments of homologous proteins of similar three-dimensional structure in the structural classification of proteins (SCOP) database to obtain a structural equivalence of residues. These equivalences are used to extend multiply aligned sequences obtained by standard sequence searches. The resulting large superfamily-based multiple alignment is converted into a PSSM. Combined with secondary structure matching and solvation potentials, 3D-PSSM can recognise structural and functional relationships beyond state-of-the-art sequence methods. In a cross-validated benchmark on 136 homologous relationships unambiguously undetectable by position-specific iterated basic local alignment search tool (PSI-Blast), 3D-PSSM can confidently assign 18 %. The method was applied to the remaining unassigned regions of the Mycoplasma genitalium genome and an additional 13 regions were assigned with 95 % confidence. 3D-PSSM is available to the community as a web server: http://www.bmm.icnet.uk/servers/3dpssm
Algorithms↗
SAWTED: structure assignment with text description--enhanced detection of remote homologues with automated SWISS-PROT annotation comparisons.
MOTIVATION: Sequence database search methods often identify putative sub-threshold hits of known function or structure for a given query sequence. It is widespread practice to filter these hits by hand using knowledge of function and other factors; to the expert, some hits may appear more sensible than others. SAWTED (Structure Assignment With Text Description) is an automated solution to this post-filtering problem which will be applicable to large scale genome assignments. RESULTS: A standard document comparison algorithm is applied to text descriptions extracted from SWISS-PROT annotations. The added value of SAWTED in combination with PSI-BLAST has been shown with a benchmark of difficult remote homologues taken from the SCOP structure database. AVAILABILITY: A WAWTED PSI-BLAST Web server is available to perform sensitive searches against the protein structure database (http://www.bmm.icnet.uk/servers/sawted). CONTACT: R.MacCallum@icrf.icnet.uk
Algorithms↗
In neck to neck competition are women more fragile?
Recent studies indicate numerous differences between female and male athletes regarding injuries of the upper and lower extremities. Studies have been much less clear concerning a gender differential regarding injuries of the cervical spine. For the purposes of the current review, injuries have been divided into three categories. The first category is cervical strain injury. It has been reported that strain injuries are more prevalent in female athletes than male athletes. The second category is cervical disc injury and cervical disc herniation. It has been reported that the male to female incidence is approximately equal in this category. In the third category, which is referred to as major structural injury, studies to date have almost entirely reported on injuries in males showing a significant male preponderance. With increasing participation of women in contact sports that cause major structural injury, a greater incidence of these injuries may be seen in women.
Athletic Injuries↗
CAFASP-1: critical assessment of fully automated structure prediction methods.
The results of the first Critical Assessment of Fully Automated Structure Prediction (CAFASP-1) are presented. The objective was to evaluate the success rates of fully automatic web servers for fold recognition which are available to the community. This study was based on the targets used in the third meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP-3). However, unlike CASP-3, the study was not a blind trial, as it was held after the structures of the targets were known. The aim was to assess the performance of methods without the user intervention that several groups used in their CASP-3 submissions. Although it is clear that "human plus machine" predictions are superior to automated ones, this CAFASP-1 experiment is extremely valuable for users of our methods; it provides an indication of the performance of the methods alone, and not of the "human plus machine" performance assessed in CASP. This information may aid users in choosing which programs they wish to use and in evaluating the reliability of the programs when applied to their specific prediction targets. In addition, evaluation of fully automated methods is particularly important to assess their applicability at genomic scales. For each target, groups submitted the top-ranking folds generated from their servers. In CAFASP-1 we concentrated on fold-recognition web servers only and evaluated only recognition of the correct fold, and not, as in CASP-3, alignment accuracy. Although some performance differences appeared within each of the four target categories used here, overall, no single server has proved markedly superior to the others. The results showed that current fully automated fold recognition servers can often identify remote similarities when pairwise sequence search methods fail. Nevertheless, in only a few cases outside the family-level targets has the score of the top-ranking fold been significant enough to allow for a confident fully automated prediction. Because the goals, rules, and procedures of CAFASP-1 were different from those used at CASP-3, the results reported here are not comparable with those reported in CASP-3. Nevertheless, it is clear that current automated fold recognition methods can not yet compete with "human-expert plus machine" predictions. Finally, CAFASP-1 has been useful in identifying the requirements for a future blind trial of automated served-based protein structure prediction.
Algorithms↗
Progress in protein structure prediction: assessment of CASP3.
The third comparative assessment of techniques of protein structure prediction (CASP3) was held during 1998. This is a blind trial in which structures are predicted prior to having knowledge of the coordinates, which are then revealed to enable the assessment. Three sections at the meeting evaluated different methodologies - comparative modelling, fold recognition and ab initio methods. For some, but not all of the target coordinates, high quality models were submitted in each of these sections. There have been improvements in prediction techniques since CASP2 in 1996, most notably for ab initio methods.
Algorithms↗
OLDERADO: on-line database of ensemble representatives and domains. On Line Database of Ensemble Representatives And DOmains.
In cases where the structure of a single protein is represented by an ensemble of conformations, there is often a need to determine the common features and to choose a "representative" conformation. This occurs, for example, with structures determined by NMR spectroscopy, analysis of the trajectory from a molecular dynamics simulation, or an ensemble of structures produced by comparative modeling. We reported previously automatic methods for (1) defining the atoms with low spatial variance across an ensemble (i.e., the "core" atoms) and the domains in which these atoms lie, and (2) clustering an ensemble into conformationally related subfamilies. To extend the utility of these methods, we have developed a freely available server on the World Wide Web at http:/(/)neon.chem.le.ac.uk/olderado/. This (1) contains an automatically generated database of representative structures, core atoms, and domains determined for 449 ensembles of NMR-derived protein structures in the Protein Data Bank (PDB) in May 1997, and (2) allows the user to upload a PDB-formatted file containing the coordinates of an ensemble of structures. The server returns in real time: (1) information on the residues constituting domains: (2) the structures that constitute each conformational subfamily; and (3) an interactive java-based three-dimensional viewer to visualise the domains and clusters. Such information is useful, for example, when selecting conformations to be used in comparative modeling and when choosing parts of structures to be used in molecular replacement. Here we describe the OLDERADO server.
Computer Communication Networks↗
Explained and unexplained medical symptoms in generalized anxiety and panic disorder: relationship to the somatoform disorders.
We have examined the numbers and types of symptoms in a sample of 90 patients with generalized anxiety disorder (GAD) and 77 patients with panic disorder (PD) collected from six different sites during the conduct of a multicenter clinical trial. This information was obtained utilizing the Health Questionnaire, a 47-item self-report list of medical symptoms, patterned after the Somatization Disorder section of the Diagnostic Interview Schedule. Although the patients in this sample had a wide variety of medically explained and unexplained physical symptoms, none of them qualified for a diagnosis of somatization disorder by DSM-III-R criteria. GAD and PD patients reported remarkably similar numbers of explained and unexplained medical symptoms. The panoply of somatic symptoms presented by these patients presents a formidable diagnostic challenge for clinicians. These findings suggest that the pattern of overutilization of medical services that is well documented for PD patients may also be found for GAD patients.
Adult↗
An automated approach for defining core atoms and domains in an ensemble of NMR-derived protein structures.
A single NMR-derived protein structure is usually deposited as an ensemble containing many structures, each consistent with the restraint set used. The number of NMR-derived structures deposited in the Protein Data Bank (PDB) is increasing rapidly. In addition, many of the structures deposited in an ensemble exhibit variation in only some regions of the structure, often with the majority of the structure remaining largely invariant across the family of structures. Therefore it is useful to determine the set of atoms whose positions are 'well defined' across an ensemble (also known as the 'core' atoms). We have developed a computer program, NMRCORE, which automatically defines (i) the core atoms, and (ii) the rigid body(ies), or domain(s), in which they occur. The program uses a sorted list of the variances in individual dihedral angles across the ensemble to define the core, followed by the automatic clustering of the variances in pairwise inter-atom distances across the ensemble to define the rigid body(ies) which comprise the core. The program is freely available via the World Wide Web (http://neon.chem.le.ac.uk/nmrcore/).
Algorithms↗
Assessment and diagnosis of adult attention deficit/hyperactivity disorder.
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Adolescent↗
An automated approach for clustering an ensemble of NMR-derived protein structures into conformationally related subfamilies.
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Cluster Analysis↗
Sertraline response in adults with mental retardation and autistic disorder.
BACKGROUND: Self-injury and aggression are common reasons for urgent psychiatric referral of persons with mental retardation and autistic spectrum disorders. Although the treatment prescribed for these problems has traditionally been neuroleptic medication, serotonin reuptake inhibitors such as sertraline may result in significant clinical improvement as well as fewer side effects. METHOD: The authors administered sertraline in an open trial to nine consecutively admitted adult mentally retarded outpatients presenting with target behaviors of self-injury and/or aggression. Most patients (N = 6) were mildly or moderately mentally retarded by DSM-III-R criteria; five had comorbid autistic disorder. Prescribed dosages ranged from 25 mg to 150 mg daily, based on observed clinical responses. Clinical Global Impressions (CGI) ratings were made at baseline and again after sertraline treatment for at least 28 days. RESULTS: Sertraline led to improvement in CGI ratings of overall clinical severity in eight of nine subjects; mean +/- SD improvement in CGI ratings was 2.44 points +/- 1.67. Discontinuation of the treatment was necessary in only one patient, after 18 weeks of sertraline treatment, because of agitation and worsening of self-picking. Side effects were otherwise minimal. CONCLUSION: These findings from a clinical sample suggest that sertraline is promising in the treatment of self-injury and aggression. Double-blind controlled studies of sertraline and other serotonin reuptake inhibitors in the treatment of self-injury and aggression in patients with mental retardation and with autistic disorder are warranted.
1-Naphthylamine↗
Effects of bone mineral density on pedicle screw fixation.
STUDY DESIGN: In an attempt to evaluate the effects of bone mineral density on the quality of fixation of pedicle screws in the lumbar spine, the axial pullout force was determined and compared in normal and osteoporotic human lumbar spines. OBJECTIVES: Four techniques of screw hole preparation were evaluated. Two pedicle screw/offset laminar hook constructs also were evaluated to determine whether the adjunct fixation of the laminar hooks would improve quality of fixation to a level sufficient to allow their use in the osteoporotic lumbar spine. METHODS: Pedicle screws were inserted by one of the listed techniques into fresh frozen cadaveric human spines. The fixation strength then was evaluated by pullout on a uniaxial testing frame. RESULTS: Bone mineral density was a strong influence on axial pullout force. In normal bone, the method of screw hole preparation did not significantly affect the quality of fixation. However, in the osteoporotic spine, either an untapped screw hole or the tapping of a screw hole with a 5.5 mm tap improved the pullout force a statistically significant amount (P < 0.003). Also, a pedicle screw with offset hooks at two adjacent levels improved the fixation significantly, increasing the pullout force to twice the expected value. CONCLUSION: Pedicle screw pullout strength was highly correlated with bone mineral density. A 5.5 mm tap or preparation with a ganglion knife improved pullout strength. Use of pedicle screws in conjunction with laminar hooks at two levels improved pullout strength.
Biomechanical Phenomena↗
Seeking improvements through laboratory benchmarking. The Western North Carolina Collaborative Group.
The laboratory departments at six North Carolina hospitals have formed an ongoing benchmarking team that has been meeting on a regular basis for more than 2 years. This article describes how the laboratory managers on this multihospital team have learned the benchmarking process, standardized procedural cost accounting in the group, compared and reduced costs, improved quality and efficiency, and created networking channels with other health-care professionals. The team members have quantified and reported significant savings and increased revenue for their laboratories as a direct result of their participation in this project.
Cost Savings↗