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Results for “Structural validation”

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At least 955 records · Page 53Linked to original sources
PubMed2002

Expression profiling reveals metabolic and structural components of extraocular muscles.

The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.

Animals↗
PubMedDate not supplied

Rational selection of training and test sets for the development of validated QSAR models.

Quantitative Structure-Activity Relationship (QSAR) models are used increasingly to screen chemical databases and/or virtual chemical libraries for potentially bioactive molecules. These developments emphasize the importance of rigorous model validation to ensure that the models have acceptable predictive power. Using k nearest neighbors (kNN) variable selection QSAR method for the analysis of several datasets, we have demonstrated recently that the widely accepted leave-one-out (LOO) cross-validated R2 (q2) is an inadequate characteristic to assess the predictive ability of the models [Golbraikh, A., Tropsha, A. Beware of q2! J. Mol. Graphics Mod. 20, 269-276, (2002)]. Herein, we provide additional evidence that there exists no correlation between the values of q2 for the training set and accuracy of prediction (R2) for the test set and argue that this observation is a general property of any QSAR model developed with LOO cross-validation. We suggest that external validation using rationally selected training and test sets provides a means to establish a reliable QSAR model. We propose several approaches to the division of experimental datasets into training and test sets and apply them in QSAR studies of 48 functionalized amino acid anticonvulsants and a series of 157 epipodophyllotoxin derivatives with antitumor activity. We formulate a set of general criteria for the evaluation of predictive power of QSAR models.

Algorithms↗
PubMed2006

A model structure for the heterodimer apoA-IMilano-apoA-II supports its peculiar susceptibility to proteolysis.

In this study, we propose a structure for the heterodimer between apolipoprotein A-I(Milano) and apolipoprotein A-II (apoA-I(M)-apoA-II) in a synthetic high-density lipoprotein (HDL) containing L-alpha-palmitoyloleoyl phosphatidylcholine. We applied bioinformatics/computational tools and procedures, such as molecular docking, molecular and essential dynamics, starting from published crystal structures for apolipoprotein A-I and apolipoprotein A-II. Structural and energetic analyses onto the simulated system showed that the molecular dynamics produced a stabilized synthetic HDL. The essential dynamic analysis showed a deviation from the starting belt structure. Our structural results were validated by limited proteolysis experiments on HDL from apoA-I(M) carriers in comparison with control HDL. The high sensitivity of apoA-I(M)-apoA-II to proteases was in agreement with the high root mean-square fluctuation values and the reduction in secondary structure content from molecular dynamics data. Circular dichroism on synthetic HDL containing apoA-I(M)-apoA-II was consistent with the alpha-helix content computed on the proposed model.

Apolipoprotein A-I↗
PubMed2003

Modular organization of cellular networks.

We investigated the organization of interacting proteins and protein complexes into networks of modules. A network-clustering method was developed to identify modules. This method of network-structure determination was validated by clustering known signaling-protein modules and by identifying module rudiments in exclusively high-throughput protein-interaction data with high error frequencies and low coverage. The signaling network controlling the yeast developmental transition to a filamentous form was clustered. Abstraction of a modular network-structure model identified module-organizer proteins and module-connector proteins. The functions of these proteins suggest that they are important for module function and intermodule communication.

Cell Communication↗
PubMed2004

"Reasons For Living"--translation, psychometric evaluation and relationships to suicidal behaviour in a Swedish random sample.

The protective role of positive beliefs and expectations against suicide has been studied using the Reasons For Living inventory (RFL). The RFL has shown to be useful in research and suggested for use in clinical practice. A Swedish translation of the RFL was examined for psychometric properties, reliability, latent structure and convergent validity in a Swedish general population. The RFL was distributed with the Suicide Behaviors Questionnaire (SBQ) to 1,366 randomly selected subjects aged 20-65 years in the county of östergötland. The results were based on 506 complete replies. The Cronbach alpha of the total RFL was 0.92, ranging from 0.72 to 0.93 in the six scales of RFL. The intercorrelations between the scales were weak and the scale to total RFL score moderate to high. The factor structure and item loadings of the inventory showed great similarities with the American one with exception for the scales Responsibility to Family and Child-related Concerns, which formed one common factor. The convergent validity was supported by significant relationships to the items of the SBQ. It is concluded that the Swedish translation of the RFL inventory in a Swedish general sample possesses great similarities to the American original RFL. Thus, it is suggested as an instrument for research and clinical usage in Sweden.

Adaptation, Psychological↗
PubMed2005

A test of enhancing model accuracy in high-throughput crystallography.

The high throughput of structure determination pipelines relies on increased automation and, consequently, a reduction of time spent on interactive quality control. In order to meet and exceed current standards in model accuracy, new approaches are needed for the facile identification and correction of model errors during refinement. One such approach is provided by the validation and structure-improvement tools of the MOL: PROBITY: web service. To test their effectiveness in high-throughput mode, a large subset of the crystal structures from the SouthEast Collaboratory for Structural Genomics (SECSG) has used protocols based on the MOL: PROBITY: tools. Comparison of 29 working-set and 19 control-set SECSG structures shows that working-set outlier scores for updated Ramachandran-plot, sidechain rotamer, and all-atom steric criteria have been improved by factors of 5- to 10-fold (relative to the control set or to a Protein Data Bank sample), while quality of covalent geometry, R(work), R(free), electron density and difference density are maintained or improved. Some parts of this correction process are already fully automated; other parts involve manual rebuilding of conformations flagged by the tests as trapped in the wrong local minimum, often altering features of functional significance. The ease and effectiveness of this technique shows that macromolecular crystal structures from either traditional or high-throughput determinations can feasibly reach a new level of excellence in conformational accuracy and reliability.

Crystallography, X-Ray↗
PubMed2006

Quadruplex DNA: sequence, topology and structure.

G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes.

Animals↗
PubMed2000

Quality of life in psychiatry: a systematic contribution to construct validation and the development of the integrative assessment tool "modular system for quality of life".

The aim of the present study is to contribute to an ongoing validation process of the Quality of Life (QoL) construct in the clinical field by investigating its internal structure. Eight (inter)nationally validated questionnaires have been analyzed by an integrative approach in a multicenter study. Data has been collected in a mentally healthy (n = 479), a depressed (n = 171) and a schizophrenic (n = 139) sample. Apart from conventional psychometric criteria a similarity structure analysis (SSA) within a facet analytic methodology has been applied. A dimensional structure of the resulting integrative questionnaire "Modular System for Quality of Life" (MSQoL) could be generated that consists of one "G-factor" (life in general) and six specific dimensions (physical health, vitality, psychosocial relationships, material resources, affect, leisure time). This basic structure represents a core module measured by 47 items which is sufficiently valid for all three samples. The empirical structures of healthy, depressed and schizophrenic samples fulfill the first law of attitude and share a common variance of 95%. In addition, there are four specific modules (demography, family, partnership, profession). No specific modules could be identified for the psychopathological subgroups. The conclusion can be drawn that QoL is construed very similar by all three investigated populations which is the base for searching for quantitative differences and profiles. The MSQoL integrates the non-redundant components of eight QoL-instruments, is psychometrically able to assess the basic structure and can be completed within a cumulative research design by items specific for a particular setting.

Adolescent↗
PubMed2006

The Illness/Injury Sensitivity Index: an examination of construct validity.

The 11-item Illness/Injury Sensitivity Index [ISI; Taylor, 1993: J Behav Ther Exp Psychiatry 24:289-299] measures fears of injury and illness and has the potential to delineate some mechanisms underlying anxiety-associated chronic health conditions. In a principal components analysis in 2005, Carleton et al. [2005a: J Psychopathol Behav Assess 27:235-241] indicated that a two-factor solution (Fear of Injury and Fear of Illness) best explained the structure of the ISI. The primary purpose of this study was to examine the structural and construct validity of the ISI. Results supported a two-factor solution after removal of two overinclusive items. Although the measure demonstrated good factorial validity, convergent and discriminant validity require further evaluation. In addition, a substantial correlation with fear of pain suggests a shift in our perspective on what constitutes a fundamental fear. Future research implications are discussed.

Adolescent↗
PubMed2003

Multi-way PLS modeling of structure-activity data by incorporating electrostatic and lipophilic potentials on molecular surface.

We devised and elaborated a surface-based three-dimensional-quantitative structure-activity relationship (3D-QSAR) method, which had been proposed in the previous study. This approach can be applied to more general case where both the electrostatic and lipophilic potentials on molecular surface simultaneously change. The 3D coordinates of all sampling points on molecular surface are projected into a 2D map by Kohonen neural network (KNN). Each node in the map is coded by the associated molecular electrostatic potential (MEP) or molecular lipophilic potential (MLP) values. The electrostatic and lipophilic KNN maps are generated for each compound and the four-way array is constructed by collecting two KNN maps of all samples. The correlation between four-way array and biological activity is examined by four-way partial least-squares (PLS). For validation, the structure-activity data of estrogen receptor antagonists was investigated. The four-way PLS model gave the high statistics at calibration and validation stages. The coefficients of the four-way PLS model back-projected on molecular surface had a reasonable 3D distribution and it was nicely consistent with active site of the estrogen receptor which was recently made clear by X-ray crystallography.

Journal Article↗
PubMedDate not supplied

A multidimensional measure of fatigue for use with cancer patients.

PURPOSE: The purpose of this study was to develop and validate a multidimensional measure of fatigue for use with cancer patients. DESCRIPTION OF STUDY: Items for the Multidimensional Fatigue Symptom Inventory (MFSI) were generated through literature review, discussion with healthcare providers, and a survey of currently available measures of fatigue. The 83-item MFSI was designed to assess global, somatic, affective, cognitive, and behavioral symptoms of fatigue. The instrument was administered on three occasions to 275 women who had received or were undergoing treatment for breast cancer and 70 women with no history of cancer. Reliability, validity, and factorial structure of the MFSI were analyzed. RESULTS: The factor analysis produced five empirically derived scales that correspond generally to the five rationally derived scales. Reliability of the rationally and empirically derived scales was excellent (alpha coefficients .87 to .96). Estimates of test-retest reliability were also favorable. Other results support the validity of both the rationally and empirically derived scales. The MFSI appears to be sensitive to fatigue, accurately discriminating cancer patients from control subjects and between patients with varying levels of performance status. CLINICAL IMPLICATIONS: The MFSI may be useful in identifying patterns of fatigue within individual patients and across treatment modalities. Such specificity may allow the clinician to develop, implement, and evaluate interventions that are targeted for differing patterns of fatigue. Because the measure is keyed to a 1-week time frame, it may be useful during the course of cancer treatment. The MFSI appears to be a valid and reliable tool to assess the full spectrum of symptoms that characterize the construct of fatigue.

Adult↗
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↗
PubMedDate not supplied

Health care providers' attitudes and beliefs towards common low back pain: factor structure and psychometric properties of the HC-PAIRS.

OBJECTIVE: The factor structure, reliability and validity of the Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS) were determined in the current study. Furthermore, the ability of the HC-PAIRS to serve as a predictor for work and activity recommendations of paramedical health care providers was examined. DESIGN: For the current study, 156 therapists from several paramedical disciplines (mostly physiotherapy, manual therapy, chiropractic, and McKenzie) completed the HC-PAIRS and questionnaires measuring the perceived harmfulness of physical activities. Furthermore, the therapists gave recommendations for work and physical activity for patients described in vignettes. Since a factor structure was already known for the HC-PAIRS a confirmatory factor analysis was carried out. Reliability of the HC-PAIRS was determined by computing Cronbach's alpha. Validity was examined by reviewing associations between scores on the HC-PAIRS and scores on measures of the harmfulness of physical activities and recommendations for work and physical activity. Regression analyses were carried out to determine whether scores on the HC-PAIRS were a predictor of recommendations for work and physical activity while controlling for other variables. RESULTS: In contrast to previous research, factor analysis revealed only 1 factor and suggested that 2 items should be removed from the HC-PAIRS. This factor had a Cronbach's alpha of 0.84. The HC-PAIRS showed adequate validity. All associations between scores on the HC-PAIRS and scores on measures of the harmfulness of physical activities and recommendations for work and physical activity were in the expected directions and ranged between 0.25 and 0.62 (P < 0.01). Scores on the HC-PAIRS were the only significant predictor of recommendations for work and physical activity when controlling for possible confounders including gender, years of experience in the treatment of back pain, judgments of severity of symptoms, and judgments of severity of pathology. CONCLUSION: The HC-PAIRS appears to be a reliable and valid measure of health care providers' attitudes and beliefs about the relationship between pain and impairment. The role of health care providers' attitudes in the treatment of low back pain is discussed.

Activities of Daily Living↗
PubMed2000

Estimation of fuzzy structure parameters for continuous junctions

The fuzzy structure theory introduced 15 years ago is designed to predict the frequency response functions of structures and structural acoustic systems with structural complexity, in the low- and medium-frequency ranges. This paper constitutes a first validation of the fuzzy structure theory for continuous junctions between the master structure and the fuzzy substructures. In addition, a method to estimate the fuzzy structure parameters introduced in the fuzzy structure theory is presented and it is validated for the case of continuous junctions. This validation obtained by numerical simulations opens the field of experimental identifications.

Journal Article↗
PubMed2004

Psychometric properties and factor structure of the Neuropsychiatric Inventory Nursing Home version in an elderly neuropsychiatric population.

BACKGROUND: The Neuropsychiatric Inventory (NPI) is an interview-based instrument designed to elicit information from an informal caregiver to evaluate behavioral disturbances in persons with dementia. Minor modifications of this instrument have produced the Neuropsychiatric Inventory-Nursing Home version (NPI-NH), a version specifically designed for interviewing professional care facility staff. The purpose of this investigation is to further understand the psychometric properties of the NPI-NH by examining its reliability, validity, and factor structure in an elderly neuropsychiatric population. METHOD: Participants were 204 elderly inpatients from a large provincial neuropsychiatric hospital in British Columbia, Canada. Data were collected as part of a patient needs assessment project. RESULTS: The internal consistency reliability of the NPI-NH was alpha=0.67. An exploratory principal axis analysis with varimax rotation revealed five factors that accounted for 63.2% of the variance. These factors reflect aspects of psychiatric disturbance associated with: (a) Agitation; (b) Mood; (c) Psychosis; (d) Sleep/Motor Activity; and (e) Elevated Behavior. Convergent and discriminant validity of the five factors by correlating them with other behavioral measures was considered satisfactory. CONCLUSIONS: These results provide support for the clinical use of the NPI-NH as a screen for neuropsychiatric symptoms in an elderly neuropsychiatric population. However, additional research is encouraged to further evaluate the clinical utility of the NPI-NH in nursing home and inpatient geriatric settings.

Adult↗
PubMed2005

A novel computational method for real-time preoperative assessment of primary dental implant stability.

A novel methodology which allows for fast and fully automatic structural analysis during preoperative planning for dental implant surgery is presented. This method integrates a fully automatic fast finite element solver within the framework of new concepts in computer-assisted preoperative planning for implant surgery. The planning system including optimized structural planning was validated by experimental results. Nine implants were placed in pig mandibles and mechanically loaded using a testing rig. The resulting displacements were measured and compared with those predicted by numerical analysis during planning. The results show that there were no statistically significant differences (P = 0.65) between the results of the models and the experiments. The results show that fast structural analysis can be integrated with surgical planning software allowing the initial axial implant stability to be predicted in real time during planning. It is believed that such a system could be used to select patients for immediate implant loading and, when further developed, be useful in other areas of preoperative surgical planning.

Animals↗
PubMed1999

Modularity and homology: modelling of the type II module family from titin.

We report the homology modelling of the structures of the 162 type II modules from the giant multi-domain protein titin (also known as connectin). The package MODELLER was used and implemented in an automated fashion using four experimentally determined structures as templates. Validation of the models was assessed in terms of divergence from the templates and consensus of the alignments. The homology within the whole family of type II modules as well as with the templates is relatively high (20-35% identity and ca 50% similarity). Comparison between the models of domains for which an NMR structure has been solved and the experimental solution gives an estimate of the quality of the modelling. Our results allow us to distinguish between a set of structurally relevant residues, which are conserved throughout the whole family and buried in the hydrophobic core, from the residues that are conserved and exposed. These latter residues are potentially functionally important. Comparison of exposed conserved patches for modules in different regions of the titin molecule suggests potential interaction surfaces. Our results may be tested directly for those modules whose binding partner is known.

Amino Acid Sequence↗
PubMed2003

Psychometric characteristics of the General Well-Being Schedule (GWB) with African-American women.

The General Well-Being Schedule (GWB) is a brief, reliable, and valid instrument used in population studies to assess psychological well-being, although its validity with African-Americans has yet to be established. This study evaluated the reliability, validity, and factor structure of the GWB in a sample of 599 overweight African-American women who participated in multicenter weight loss trial. The results of the factor analysis indicate that the GWB is primarily unidimensional and that the existence of the six hypothesized subscales was not supported. The GWB demonstrated evidence of concurrent and construct validity when examined in association with measures of self-concept, depression, and several health behaviors. The results of this study suggest that the GWB is a reliable and valid measure of psychological well-being in African-American women.

Adult↗