A major quantitative trait locus for CD4-CD8 ratio is located on chromosome 11

CD4-CD8 ratio is an important diagnostic measure of immune system functioning. In particular, CD4-CD8 ratio predicts the time taken for progression of HIV infection to acquired immune deficiency syndrome (AIDS) and the long-term survival of AIDS patients. To map genes that regulate differences between healthy individuals in CD4-CD8 ratio, we typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 cM across the genome in 405 pairs of dizygotic twins at ages 12, 14 and 16. We used multipoint variance components linkage analysis to test for linkage between marker loci and CD4-CD8 ratio at each age. We found suggestive evidence of linkage on chromosome 11p in 12-year-old twins (LOD=2.55, P=0.00031) and even stronger evidence of linkage in the same region at age 14 (LOD 3.51, P=0.00003). Possible candidate genes include CD5 and CD6, which encode cell membrane proteins involved in the positive selection of thymocytes. We also found suggestive evidence of linkage at other areas of the genome including regions on chromosomes 1, 3, 4, 5, 6, 12, 13, 15, 17 and 22.

Major quantitative trait locus for eosinophil count is located on chromosome 2q

Background: Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs. 1 Objective: To identify QTLs responsible for variation in eosinophil count in adolescent twins. Methods: We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome. Results: We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds = 4.6; P = .000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds = 1.0; P = .016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22. Conclusion: A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.

California older adult Stroop test (COAST): Development of a Stroop test adapted for geriatric populations

An adaptation of the traditional Stroop test, the California Older Adult Stroop Test (COAST) (Pachana, Marcopulos, Yoash-Gantz & Thompson, 1995), has been developed specifically for use with a geriatric population, utilizing larger typeface, fewer items (50) per task, and more easily distinguished colors (red, yellow and green). Test-retest reliability and validity data are reviewed for both control and clinical populations. Increased error rates on the Stroop test compared to the COAST were found for the color and color/word interference tasks. These results are discussed in terms of changes in the visual system with increasing age. The implications for better test sensitivity with the COAST for older adult populations are discussed.

Specialization in pyramidal cell structure in the sensory-motor cortex of the vervet monkey (Cercopethicus pygerythrus)

Recent studies have revealed systematic differences in the pyramidal cell structure between functionally related cortical areas of primates. Trends for a parallel in pyramidal cell structure and functional complexity have been reported in visual, somatosensory, motor, cingulate and prefrontal cortex in the macaque monkey cortex. These specializations in structure have been interpreted as being fundamental in determining cellular and systems function, endowing circuits in these different cortical areas with different computational power. In the present study we extend our initial finding of systematic specialization of pyramidal cell structure in sensory-motor cortex in the macaque monkey [Cereb Cortex 12 (2002) 1071] to the vervet monkey. More specifically, we investigated pyramidal cell structure in somatosensory and motor areas 1/2, 5, 7, 4 and 6. Neurones in fixed, flat-mounted, cortical slices were injected intracellularly with Lucifer Yellow and processed for a light-stable 3,3'-diaminobenzidine reaction product. The size of, number of branches in, and spine density of the basal dendritic arbors varied systematically such that there was a trend for increasing complexity in arbor structure with progression through 1/2, 5 and 7. In addition, cells in area 6 were larger, more branched, and more spinous than those in area 4. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.

Animal visual systems and the evolution of color patterns: Sensory processing illuminates signal evolution

Animal color pattern phenotypes evolve rapidly. What influences their evolution? Because color patterns are used in communication, selection for signal efficacy, relative to the intended receiver's visual system, may explain and predict the direction of evolution. We investigated this in bowerbirds, whose color patterns consist of plumage, bower structure, and ornaments and whose visual displays are presented under predictable visual conditions. We used data on avian vision, environmental conditions, color pattern properties, and an estimate of the bowerbird phylogeny to test hypotheses about evolutionary effects of visual processing. Different components of the color pattern evolve differently. Plumage sexual dimorphism increased and then decreased, while overall (plumage plus bower) visual contrast increased. The use of bowers allows relative crypsis of the bird but increased efficacy of the signal as a whole. Ornaments do not elaborate existing plumage features but instead are innovations (new color schemes) that increase signal efficacy. Isolation between species could be facilitated by plumage but not ornaments, because we observed character displacement only in plumage. Bowerbird color pattern evolution is at least partially predictable from the function of the visual system and from knowledge of different functions of different components of the color patterns. This provides clues to how more constrained visual signaling systems may evolve.

Is the method of signal analysis and test selection important for measuring standing balance in subjects with persistent whiplash?

Dizziness and or unsteadiness, associated with episodes of loss of balance, are frequent complaints in those suffering from persistent problems following a whiplash injury. Research has been inconclusive with respect to possible aetiology, discriminative tests and analyses used. The aim of this pilot research was to identify the test conditions and the most appropriate method for the analysis of sway that may differentiate subjects with persistent whiplash associated disorders (WAD) from healthy controls. The six conditions of the Clinical Test for Sensory Interaction in Balance was performed in both comfortable and tandem stance in 20 subjects with persistent WAD compared to 20 control subjects. The analyses were carried out using a traditional method of measurement, total sway distance, to results obtained from the use of wavelet analysis. Subjects with WAD were significantly less able to complete the tandem stance tests on a firm surface than controls. In comfortable stance, using wavelet analysis, significant differences between subjects with WAD and the control group were evident in total energy of the trace for all test conditions apart from eyes open on the firm surface. In contrast, the results of the analysis using total sway distance revealed no significant differences between groups across all six conditions. Wavelet analysis may be more appropriate for detecting disturbances in balance in whiplash subjects because the technique allows separation of the noise from the underlying systematic effect of sway. These findings will be used to direct future studies on the aeitiology of balance disturbances in WAD. (c) 2004 Elsevier B.V. All rights reserved.

Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score > 2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

A linkage study of academic skills defined by the Queensland Core Skills Test

This study used genome-wide linkage analysis to detect Quantitative Trait Loci (QTLs) implicated in variation in general academic achievement as measured by the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2004). Data from 210 families were analysed. While no empirically derived significant or suggestive peaks for general academic achievement were indicated a peak on chromosome 2 was observed in a region where Posthuma et al. (2005) reported significant linkage for Performance IQ (PIQ) and suggestive linkage for Full Scale IQ (FSIQ), and Luciano et al. (this issue) observed significant linkage for PIQ and word reading. A peak on chromosome 18 was also observed approximately 20 cM removed from a region recently implicated in reading achievement. In addition, on chromosomes 2 and 18 peaks for a number of specific academic skills, two of which were suggestive, coincided with the general academic achievement peaks. The findings suggest that variation in general academic achievement is influenced by genes on chromosome 2 which have broad influence on a variety of cognitive abilities.

The design of environmental test rigs

Product reliability and its environmental performance have become critical elements within a product's specification and design. To obtain a high level of confidence in the reliability of the design it is customary to test the design under realistic conditions in a laboratory. The objective of the work is to examine the feasibility of designing mechanical test rigs which exhibit prescribed dynamical characteristics. The design is then attached to the rig and excitation is applied to the rig, which then transmits representative vibration levels into the product. The philosophical considerations made at the outset of the project are discussed as they form the basis for the resulting design methodologies. It is attempted to directly identify the parameters of a test rig from the spatial model derived during the system identification process. It is shown to be impossible to identify a feasible test rig design using this technique. A finite dimensional optimal design methodology is developed which identifies the parameters of a discrete spring/mass system which is dynamically similar to a point coordinate on a continuous structure. This design methodology is incorporated within another procedure which derives a structure comprising a continuous element and a discrete system. This methodology is used to obtain point coordinate similarity for two planes of motion, which is validated by experimental tests. A limitation of this approach is that it is impossible to achieve multi-coordinate similarity due to an interaction of the discrete system and the continuous element at points away from the coordinate of interest. During the work the importance of the continuous element is highlighted and a design methodology is developed for continuous structures. The design methodology is based upon distributed parameter optimal design techniques and allows an initial poor design estimate to be moved in a feasible direction towards an acceptable design solution. Cumulative damage theory is used to provide a quantitative method of assessing the quality of dynamic similarity. It is shown that the combination of modal analysis techniques and cumulative damage theory provides a feasible design synthesis methodology for representative test rigs.

Quantitative optical coherence tomography for characterization of microscopic structures with varying refractive index

In this paper we have done back to back comparison of quantitive phase and refractive index from a microscopic image of waveguide previously obtained by Allsop et al. Paper also shows microscopic image of the first 3 waveguides from the sample. Tomlins et al. have demonstrated use of femtosecond fabricated artefacts as OCT calibration samples. Here we present the use of femtosecond waveguides, inscribed with optimized parameters, to test and calibrate the sensitivity of the OCT systems.

Premonitory urges for tics in adult patients with Tourette syndrome

Objective: Patients with Tourette syndrome (TS) often report characteristic sensory experiences, also called premonitory urges (PUs), which precede tic expression and have high diagnostic relevance. This study investigated the usefulness of a scale developed and validated in children and adolescents-the Premonitory Urge for Tics Scale (PUTS, Woods et al., 2005 [13])-for the assessment of PUs in adult patients with TS. Method: Standard statistical methods were applied to test the psychometric properties of the PUTS in 102 adult TS outpatients recruited from two specialist clinics in the United Kingdom. Results: The PUTS showed good acceptability and endorsement rates, with evenly distributed scores and low floor and ceiling effects. Item-total correlations were moderate to strong; PUTS total scores were significantly correlated with quantitative measures of TS severity. The PUTS showed excellent internal consistency reliability (Cronbach's alpha=0.85) and Spearman's correlations demonstrated satisfactory convergent and discriminant validity. Conclusions: Although originally devised to assess urges to tic in young patients with TS, the PUTS demonstrated good psychometric properties in a large sample of adults recruited at specialist TS clinics. This instrument is therefore recommended for use across the life span as a valid and reliable self-report measure of sensory experiences accompanying tic expression. © 2013 The Japanese Society of Child Neurology.

Quantitative optical coherence tomography for characterization of microscopic structures with varying refractive index

In this paper we have done back to back comparison of quantitive phase and refractive index from a microscopic image of waveguide previously obtained by Allsop et al. Paper also shows microscopic image of the first 3 waveguides from the sample. Tomlins et al. have demonstrated use of femtosecond fabricated artefacts as OCT calibration samples. Here we present the use of femtosecond waveguides, inscribed with optimized parameters, to test and calibrate the sensitivity of the OCT systems.

Peptide binding to HLA-DP proteins at pH 5.0 and pH 7.0:a quantitative molecular docking study

Background: HLA-DPs are class II MHC proteins mediating immune responses to many diseases. Peptides bind MHC class II proteins in the acidic environment within endosomes. Acidic pH markedly elevates association rate constants but dissociation rates are almost unchanged in the pH range 5.0 - 7.0. This pH-driven effect can be explained by the protonation/deprotonation states of Histidine, whose imidazole has a pKa of 6.0. At pH 5.0, imidazole ring is protonated, making Histidine positively charged and very hydrophilic, while at pH 7.0 imidazole is unprotonated, making Histidine less hydrophilic. We develop here a method to predict peptide binding to the four most frequent HLA-DP proteins: DP1, DP41, DP42 and DP5, using a molecular docking protocol. Dockings to virtual combinatorial peptide libraries were performed at pH 5.0 and pH 7.0. Results: The X-ray structure of the peptide - HLA-DP2 protein complex was used as a starting template to model by homology the structure of the four DP proteins. The resulting models were used to produce virtual combinatorial peptide libraries constructed using the single amino acid substitution (SAAS) principle. Peptides were docked into the DP binding site using AutoDock at pH 5.0 and pH 7.0. The resulting scores were normalized and used to generate Docking Score-based Quantitative Matrices (DS-QMs). The predictive ability of these QMs was tested using an external test set of 484 known DP binders. They were also compared to existing servers for DP binding prediction. The models derived at pH 5.0 predict better than those derived at pH 7.0 and showed significantly improved predictions for three of the four DP proteins, when compared to the existing servers. They are able to recognize 50% of the known binders in the top 5% of predicted peptides. Conclusions: The higher predictive ability of DS-QMs derived at pH 5.0 may be rationalised by the additional hydrogen bond formed between the backbone carbonyl oxygen belonging to the peptide position before p1 (p-1) and the protonated ε-nitrogen of His 79β. Additionally, protonated His residues are well accepted at most of the peptide binding core positions which is in a good agreement with the overall negatively charged peptide binding site of most MHC proteins. © 2012 Patronov et al.; licensee BioMed Central Ltd.

A quantitative approach to the organizational design problem

The span of control is the most discussed single concept in classical and modern management theory. In specifying conditions for organizational effectiveness, the span of control has generally been regarded as a critical factor. Existing research work has focused mainly on qualitative methods to analyze this concept, for example heuristic rules based on experiences and/or intuition. This research takes a quantitative approach to this problem and formulates it as a binary integer model, which is used as a tool to study the organizational design issue. This model considers a range of requirements affecting management and supervision of a given set of jobs in a company. These decision variables include allocation of jobs to workers, considering complexity and compatibility of each job with respect to workers, and the requirement of management for planning, execution, training, and control activities in a hierarchical organization. The objective of the model is minimal operations cost, which is the sum of supervision costs at each level of the hierarchy, and the costs of workers assigned to jobs. The model is intended for application in the make-to-order industries as a design tool. It could also be applied to make-to-stock companies as an evaluation tool, to assess the optimality of their current organizational structure. Extensive experiments were conducted to validate the model, to study its behavior, and to evaluate the impact of changing parameters with practical problems. This research proposes a meta-heuristic approach to solving large-size problems, based on the concept of greedy algorithms and the Meta-RaPS algorithm. The proposed heuristic was evaluated with two measures of performance: solution quality and computational speed. The quality is assessed by comparing the obtained objective function value to the one achieved by the optimal solution. The computational efficiency is assessed by comparing the computer time used by the proposed heuristic to the time taken by a commercial software system. Test results show the proposed heuristic procedure generates good solutions in a time-efficient manner.

The utility of an Integrated Qualitative /Quantitative Data Analytic Strategy (IQ -DAS) to evaluate the impact of youth development interventions to positive qualitative change in the life course

This study reports one of the first controlled studies to examine the impact of a school based positive youth development program (Lerner, Fisher, & Weinberg, 2000) on promoting qualitative change in life course experiences as a positive intervention outcome. The study built on a recently proposed relational developmental methodological metanarrative (Overton, 1998) and advances in use of qualitative research methods (Denzin & Lincoln, 2000). The study investigated the use the Life Course Interview (Clausen, 1998) and an integrated qualitative and quantitative data analytic strategy (IQ-DAS) to provide empirical documentation of the impact the Changing Lives Program on qualitative change in positive identity in a multicultural population of troubled youth in an alternative public high school. The psychosocial life course intervention approach used in this study draws its developmental framework from both psychosocial developmental theory (Erikson, 1968) and life course theory (Elder, 1998) and its intervention strategies from the transformative pedagogy of Freire's (1983/1970). ^ Using the 22 participants in the Intervention Condition and the 10 participants in the Control Condition, RMANOVAs found significantly more positive qualitative change in personal identity for program participants relative to the non-intervention control condition. In addition, the 2X2X2X3 mixed design RMANOVA in which Time (pre, post) was the repeated factor and Condition (Intervention versus Control), Gender, and Ethnicity the between group factors, also found significant interactions for the Time by Gender and Time by Ethnicity. ^ Moreover, the directionality of the basic pattern of change was positive for participants of both genders and all three ethnic groups. The pattern of the moderation effects also indicated a marked tendency for participants in the intervention group to characterize their sense of self as more secure and less negative at the end of the their first semester in the intervention, that was stable across both genders and all three ethnicities. The basic differential pattern of an increase in the intervention condition of a positive characterization of sense of self relative to both pre test and relative to the directionality of the movement of the non-intervention controls, was stable across both genders and all three ethnic groups. ^