STUDIES ON THE PATTERNS OF NUCLEOTIDE AND AMINO ACID SUBSTITUTION (ELECTROPHORESIS, MUTATION RATE, SELECTION, BASE, COMPOSITION)

Theoretical and empirical studies were conducted on the pattern of nucleotide and amino acid substitution in evolution, taking into account the effects of mutation at the nucleotide level and purifying selection at the amino acid level. A theoretical model for predicting the evolutionary change in electrophoretic mobility of a protein was also developed by using information on the pattern of amino acid substitution. The specific problems studied and the main results obtained are as follows: (1) Estimation of the pattern of nucleotide substitution in DNA nuclear genomes. The pattern of point mutations and nucleotide substitutions among the four different nucleotides are inferred from the evolutionary changes of pseudogenes and functional genes, respectively. Both patterns are non-random, the rate of change varying considerably with nucleotide pair, and that in both cases transitions occur somewhat more frequently than transversions. In protein evolution, substitution occurs more often between amino acids with similar physico-chemical properties than between dissimilar amino acids. (2) Estimation of the pattern of nucleotide substitution in RNA genomes. The majority of mutations in retroviruses accumulate at the reverse transcription stage. Selection at the amino acid level is very weak, and almost non-existent between synonymous codons. The pattern of mutation is very different from that in DNA genomes. Nevertheless, the pattern of purifying selection at the amino acid level is similar to that in DNA genomes, although selection intensity is much weaker. (3) Evaluation of the determinants of molecular evolutionary rates in protein-coding genes. Based on rates of nucleotide substitution for mammalian genes, the rate of amino acid substitution of a protein is determined by its amino acid composition. The content of glycine is shown to correlate strongly and negatively with the rate of substitution. Empirical formulae, called indices of mutability, are developed in order to predict the rate of molecular evolution of a protein from data on its amino acid sequence. (4) Studies on the evolutionary patterns of electrophoretic mobility of proteins. A theoretical model was constructed that predicts the electric charge of a protein at any given pH and its isoelectric point from data on its primary and quaternary structures. Using this model, the evolutionary change in electrophoretic mobilities of different proteins and the expected amount of electrophoretically hidden genetic variation were studied. In the absence of selection for the pI value, proteins will on the average evolve toward a mildly basic pI. (Abstract shortened with permission of author.) ^

Relationship between dietary patterns and body mass index in Hispanic children ages 4--19 years of age

Background. In over 30 years, the prevalence of overweight for children and adolescents has increased across the United States (Barlow et al., 2007; Ogden, Flegal, Carroll, & Johnson, 2002). Childhood obesity is linked with adverse physiological and psychological issues in youth and affects ethnic/minority populations in disproportionate rates (Barlow et al., 2007; Butte et al., 2006; Butte, Cai, Cole, Wilson, Fisher, Zakeri, Ellis, & Comuzzie, 2007). More importantly, overweight in children and youth tends to track into adulthood (McNaughton, Ball, Mishra, & Crawford, 2008; Ogden et al., 2002). Childhood obesity affects body functions such as the cardiovascular, respiratory, gastrointestinal, and endocrine systems, including emotional health (Barlow et al., 2007, Ogden et al., 2002). Several dietary factors have been associated with the development of obesity in children; however, these factors have not been fully elucidated, especially in ethnic/minority children. In particular, few studies have been done to determine the effects of different meal patterns on the development of obesity in children. Purpose. The purpose of the study is to examine the relationships between daily proportions of energy consumed and energy derived from fat across breakfast, lunch, dinner, and snack, and obesity among Hispanic children and adolescents. Methods. A cross-sectional design was used to evaluate the relationship between dietary patterns and overweight status in Hispanic children and adolescents 4-19 years of age who participated in the Viva La Familia Study. The goal of the Viva La Familia Study was to evaluate genetic and environmental factors affecting childhood obesity and its co-morbidities in the Hispanic population (Butte et al., 2006, 2007). The study enrolled 1030 Hispanic children and adolescents from 319 families and examined factors related to increased body weight by focusing on a multilevel analysis of extensive sociodemographic, genetic, metabolic, and behavioral data. Baseline dietary intakes of the children were collected using 24-hour recalls, and body mass index was calculated from measured height and weight, and classified using the CDC standards. Dietary data were analyzed using a GEE population-averaged panel-data model with a cluster variable family identifier to include possible correlations within related data sets. A linear regression model was used to analyze associations of dietary patterns using possible covariates, and to examine the percentage of daily energy coming from breakfast, lunch, dinner, and snack while adjusting for age, sex, and BMI z-score. Random-effects logistic regression models were used to determine the relationship of the dietary variables with obesity status and to understand if the percent energy intake (%EI) derived from fat from all meals (breakfast, lunch, dinner, and snacks) affected obesity. Results. Older children (age 4-19 years) consumed a higher percent of energy at lunch and dinner and less percent energy from snacks compared to younger children. Age was significantly associated with percentage of total energy intake (%TEI) for lunch, as well as dinner, while no association was found by gender. Percent of energy consumed from dinner significantly differed by obesity status, with obese children consuming more energy at dinner (p = 0.03), but no associations were found between percent energy from fat and obesity across all meals. Conclusions. Information from this study can be used to develop interventions that target dietary intake patterns in obesity prevention programs for Hispanic children and adolescents. In particular, intervention programs for children should target dietary patterns with energy intake that is spread throughout the day and earlier in the day. These results indicate that a longitudinal study should be used to further explore the relationship of dietary patterns and BMI in this and other populations (Dubois et al., 2008; Rodriquez & Moreno, 2006; Thompson et al., 2005; Wilson et al., in review, 2008). ^

Computer simulation of random parckings for self-similar particle size distributions in soil and granular materials: porosity and pore size distribution

A 2D computer simulation method of random packings is applied to sets of particles generated by a self-similar uniparametric model for particle size distributions (PSDs) in granular media. The parameter p which controls the model is the proportion of mass of particles corresponding to the left half of the normalized size interval [0,1]. First the influence on the total porosity of the parameter p is analyzed and interpreted. It is shown that such parameter, and the fractal exponent of the associated power scaling, are efficient packing parameters, but this last one is not in the way predicted in a former published work addressing an analogous research in artificial granular materials. The total porosity reaches the minimum value for p = 0.6. Limited information on the pore size distribution is obtained from the packing simulations and by means of morphological analysis methods. Results show that the range of pore sizes increases for decreasing values of p showing also different shape in the volume pore size distribution. Further research including simulations with a greater number of particles and image resolution are required to obtain finer results on the hierarchical structure of pore space.

Aluminum-Resistant Arabidopsis Mutants That Exhibit Altered Patterns of Aluminum Accumulation and Organic Acid Release from Roots1

Al-resistant (alr) mutants of Arabidopsis thaliana were isolated and characterized to gain a better understanding of the genetic and physiological mechanisms of Al resistance. alr mutants were identified on the basis of enhanced root growth in the presence of levels of Al that strongly inhibited root growth in wild-type seedlings. Genetic analysis of the alr mutants showed that Al resistance was semidominant, and chromosome mapping of the mutants with microsatellite and random amplified polymorphic DNA markers indicated that the mutants mapped to two sites in the Arabidopsis genome: one locus on chromosome 1 (alr-108, alr-128, alr-131, and alr-139) and another on chromosome 4 (alr-104). Al accumulation in roots of mutant seedlings was studied by staining with the fluorescent Al-indicator dye morin and quantified via inductively coupled argon plasma mass spectrometry. It was found that the alr mutants accumulated lower levels of Al in the root tips compared with wild type. The possibility that the mutants released Al-chelating organic acids was examined. The mutants that mapped together on chromosome 1 released greater amounts of citrate or malate (as well as pyruvate) compared with wild type, suggesting that Al exclusion from roots of these alr mutants results from enhanced organic acid exudation. Roots of alr-104, on the other hand, did not exhibit increased release of malate or citrate, but did alkalinize the rhizosphere to a greater extent than wild-type roots. A detailed examination of Al resistance in this mutant is described in an accompanying paper (J. Degenhardt, P.B. Larsen, S.H. Howell, L.V. Kochian [1998] Plant Physiol 117: 19–27).

Analysis of a random-assignment short term rehabilitation program. Analytic study 5 and 6.

National Highway Traffic Safety Administration, Office of Driver and Pedestrian Programs, Washington, D.C.

Physical activity patterns of Singaporean adolescents

The purpose of this study was to document the level of physical activity and sedentary behavior in a representative sample of Singaporean adolescents. A random sample of 1,827 secondary school students from six secondary schools (929 boys, 898 girls, mean age 14.9 +/- 1.2 yr) completed the Three-Day Physical Activity Recall (3DPAR) self-report instrument. Approximately 63% of Singaporean high school students met current guidelines requiring 60 min of moderate to vigorous physical activity daily. Just over half (51.6%) met the guideline calling for regular vigorous physical activity. Across all grade levels, boys were consistently more active than girls. More than 70% of Singaporean high school students exceeded the recommended 2 hours per day of electronic media use. Collectively, these findings suggest that a significant proportion of Singaporean adolescents are not sufficiently active and are in need of programs to promote physical activity and decrease sedentary behavior.

Do predators aggregate in response to pest density in agroecosystems? Assessing within-field spatial patterns

1. The spatial heterogeneity of predator populations is an important component of ecological theories pertaining to predator-prey dynamics. Most studies within agricultural fields show spatial correlation (positive or negative) between mean predator numbers and prey abundance across a whole field over time but generally ignore the within-field spatial dimension. We used explicit spatial mapping to determine if generalist predators aggregated within a soybean field, the size of these aggregations and if predator aggregation was associated with pest aggregation, plant damage and predation rate. 2. The study was conducted at Gatton in the Lockyer Valley, 90 km west of Brisbane, Australia. Intensive sampling grids were used to investigate within-field spatial patterns. The first row of each grid was located in a lucerne field (10 m from interface) and the remaining rows were in an adjacent soybean field. At each point on the grid the abundance of foliage-dwelling and ground-dwelling pests and predators was measured, predation rates [using sentinel Helicoverpa armigera (Hubner) egg cards] and plant damage were estimated. Eight grids were sampled across two summer cropping seasons (2000/01, 2001/02). 3. Predators exhibited strong spatial patterning with regions of high and low abundance and activity within what are considered to be uniform soybean fields. Ground-dwelling and foliage-dwelling predators were often aggregated in patches approximately 40 m across. 4. Lycosidae (wolf spiders) displayed aggregation and were consistently more abundant within the lucerne, with a decreasing trap catch with distance from the lucrene/soybean interface. This trend was consistent between subsequent grids in a single field and between fields. 5. The large amount of spatial variability in within-field arthropod abundance (pests and predators) and activity (egg predation and plant damage) indicates that whole field averages were misleading. This result has serious implications for sampling of arthropod abundance and pest management decision-making based on scouting data. 6. There was a great deal of temporal change in the significant spatial patterns observed within a field at each sampling time point during a single season. Predator and pest aggregations observed in these fields were generally not stable for the entire season. 7. Predator aggregation did not correlate consistently with pest aggregation, plant damage or predation rate. Spatial patterns in predator abundance were not associated consistently with any single parameter measured. The most consistent positive association was between foliage-dwelling predators and pests (significant in four of seven grids). Inferring associations between predators and prey based on an intensive one-off sampling grid is difficult, due to the temporal variability in the abundance of each group. 8. Synthesis and applications. This study demonstrated that generalist predator populations are rarely distributed randomly and field edges and adjacent crops can have an influence on within-field predator abundance. This must be considered when estimating arthropod (pest and predator) abundance from a set of samples taken at random locations within a field.

Measuring the spatial arrangement patterns of pathological lesions in histological sections of brain tissue

The development of abnormal protein aggregates in the form of extracellular plaques and intracellular inclusions is a characteristic feature of many neurodegenerative diseases such as Alzheimer's disease (AD), Creutzfeldt-Jakob disease (CJD) and the fronto-temporal dementias (FTD). An important aspect of a pathological protein aggregate is its spatial topography in the tissue. Lesions may not be randomly distributed within a histological section but exhibit spatial pattern, a departure from randomness either towards regularity or clustering. Information on the spatial pattern of a lesion may be useful in elucidating its pathogenesis and in studying the relationships between different lesions. This article reviews the methods that have been used to study the spatial topography of lesions. These include simple tests of whether the distribution of a lesion departs significantly from random using randomized points or sample fields, and more complex methods that employ grids or transects of contiguous fields and which can detect the intensity of aggregation and the sizes, distribution and spacing of the clusters. The usefulness of these methods in elucidating the pathogenesis of protein aggregates in neurodegenerative disease is discussed.

On the existence of visual technical patterns in the UK stock market

The aim in this paper is to replicate and extend the analysis of visual technical patterns by Lo et al. (2000) using data on the UK market. A non-parametric smoother is used to model a nonlinear trend in stock price series. Technical patterns, such as the 'head-and-shoulders' pattern, that are characterised by a sequence of turning points are identified in the smoothed data. Statistical tests are used to determine whether returns conditioned on the technical patterns are different from random returns and, in an extension to the analysis of Lo et al. (2000), whether they can outperform a market benchmark return. For the stocks in the FTSE 100 and FTSE 250 indices over the period 1986 to 2001, we find that technical patterns occur with different frequencies to each other and in different relativities to the frequencies found in the US market. Our extended statistical testing indicates that UK stock returns are less influenced by technical patterns than was the case for US stock returns.

Spatial patterns of the tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated. © 2012 Springer-Verlag.

Changes in neural complexity during the perception of 3D images using random dot stereograms

One developing theme in consciousness research is that consciousness is not the product of any specific component of the brain, rather it is an emergent property of the changing patterns of connectivity between different specialised functional components. For example, the dynamic core hypothesis proposes that conscious experience requires high levels of neural complexity, where complexity is defined in terms of functional connectivity. To test this hypothesis, electroencephalography was recorded while participants were shown random dot-stereograms. Consistent with the dynamic core hypothesis, neural complexity increased as the participants changed from simply viewing the stereogram to consciously perceiving the hidden 3D image.

Patterns in the lottery game

The present study is based on the analysis and results of a close to 5 years’ study in the frame which we used a “Lottery Game” in the "Decision Making Skills" subject taught at Corvinus Business School, Corvinus University of Budapest. In the frame of the "game", the students (Hungarians (n=231) and foreigners (n=267) alike) have to mark 6 numbers on a 7x7 lottery ticket. The winner is the student whose numbers differ the most from those of all the other students’. Upon analyzing the results (irrespectively of nationality) the authors have noted something notable: the winning combinations - rather than being located randomly on the ticket, characteristically resemble a geometric form. In our study we wanted to detect the relevance of geometry in this kind of choices. It is hypothesized that in such games (lottery type, related to numeric combination choice), where the players decide upon their strategy (choice of numbers) by also taking into consideration others’ expected choices, the winning strategy is characteristically some consciously chosen scheme or pattern as opposed to a random one. The study presents the results of the available samples (Hungarian students: n=231, foreign students: n=267), the winning combinations, the most often designated numbers, as well as the least “popular” numbers and their presentation on a "heat map". In the case of the majority of the winning tickets we found the use of conscious strategic choice to be more useful. These conscious strategic decisions were reflected in identifiable geometric forms. Based on the results, we hypothesize that in the "hidden lottery" game – in contrast with random choice – the most effective strategy of choice is the conscious ordered one in which the player marks the numbers on the lottery ticket in some modified geometric pattern. The goal of the paper is to propose further research on the field.

Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level.

Objective. This study aims to provide a better understanding of the amounts spent on different malaria prevention products and the determinants of these expenditures. Methods. 1,601 households were interviewed about their expenditure on malaria mosquito nets in the past five years, net re-treatments in the past six months and other expenditures prevention in the past two weeks. Simple random sampling was used to select villages and streets while convenience sampling was used to select households. Expenditure was compared across bed nets, aerosols, coils, indoor spraying, using smoke, drinking herbs and cleaning outside environment. Findings. 68% of households owned at least one bed net and 27% had treated their nets in the past six months. 29% were unable to afford a net. Every fortnight, households spent an average of US $0.18 on nets and their treatment, constituting about 47% of total prevention expenditure. Sprays, repellents and coils made up 50% of total fortnightly expenditure (US$0.21). Factors positively related to expenditure were household wealth, years of education of household head, household head being married and rainy season. Poor quality roads and living in a rural area had a negative impact on expenditure. Conclusion. Expenditure on bed nets and on alternative malaria prevention products was comparable. Poor households living in rural areas spend significantly less on all forms of malaria prevention compared to their richer counterparts. Breaking the cycle between malaria and poverty is one of the biggest challenges facing malaria control programmes in Africa.

Internal Capital, External Knowledge, and Random Draws: Three Drivers of Organizational Structure

This dissertation explores the complex interactions between organizational structure and the environment. In Chapter 1, I investigate the effect of financial development on the formation of European corporate groups. Since cross-country regressions are hard to interpret in a causal sense, we exploit exogenous industry measures to investigate a specific channel through which financial development may affect group affiliation: internal capital markets. Using a comprehensive firm-level dataset on European corporate groups in 15 countries, we find that countries

with less developed financial markets have a higher percentage of group affiliates in more capital intensive industries. This relationship is more pronounced for young and small firms and for affiliates of large and diversified groups. Our findings are consistent with the view that internal capital markets may, under some conditions, be more efficient than prevailing external markets, and that this may drive group affiliation even in developed economies. In Chapter 2, I bridge current streams of innovation research to explore the interplay between R&D, external knowledge, and organizational structure–three elements of a firm’s innovation strategy which we argue should logically be studied together. Using within-firm patent assignment patterns,

we develop a novel measure of structure for a large sample of American firms. We find that centralized firms invest more in research and patent more per R&D dollar than decentralized firms. Both types access technology via mergers and acquisitions, but their acquisitions differ in terms of frequency, size, and i\ntegration. Consistent with our framework, their sources of value creation differ: while centralized firms derive more value from internal R&D, decentralized firms rely more on external knowledge. We discuss how these findings should stimulate more integrative work on theories of innovation. In Chapter 3, I use novel data on 1,265 newly-public firms to show that innovative firms exposed to environments with lower M&A activity just after their initial public offering (IPO) adapt by engaging in fewer technological acquisitions and

more internal research. However, this adaptive response becomes inertial shortly after IPO and persists well into maturity. This study advances our understanding of how the environment shapes heterogeneity and capabilities through its impact on firm structure. I discuss how my results can help bridge inertial versus adaptive perspectives in the study of organizations, by

documenting an instance when the two interact.

Spatial Relationships among Hydroacoustic, Hydrographic and Top Predator Patterns: Cetacean Distributions in the Mid-Atlantic Bight

Effective conservation and management of top predators requires a comprehensive understanding of their distributions and of the underlying biological and physical processes that affect these distributions. The Mid-Atlantic Bight shelf break system is a dynamic and productive region where at least 32 species of cetaceans have been recorded through various systematic and opportunistic marine mammal surveys from the 1970s through 2012. My dissertation characterizes the spatial distribution and habitat of cetaceans in the Mid-Atlantic Bight shelf break system by utilizing marine mammal line-transect survey data, synoptic multi-frequency active acoustic data, and fine-scale hydrographic data collected during the 2011 summer Atlantic Marine Assessment Program for Protected Species (AMAPPS) survey. Although studies describing cetacean habitat and distributions have been previously conducted in the Mid-Atlantic Bight, my research specifically focuses on the shelf break region to elucidate both the physical and biological processes that influence cetacean distribution patterns within this cetacean hotspot.

In Chapter One I review biologically important areas for cetaceans in the Atlantic waters of the United States. I describe the study area, the shelf break region of the Mid-Atlantic Bight, in terms of the general oceanography, productivity and biodiversity. According to recent habitat-based cetacean density models, the shelf break region is an area of high cetacean abundance and density, yet little research is directed at understanding the mechanisms that establish this region as a cetacean hotspot.

In Chapter Two I present the basic physical principles of sound in water and describe the methodology used to categorize opportunistically collected multi-frequency active acoustic data using frequency responses techniques. Frequency response classification methods are usually employed in conjunction with net-tow data, but the logistics of the 2011 AMAPPS survey did not allow for appropriate net-tow data to be collected. Biologically meaningful information can be extracted from acoustic scattering regions by comparing the frequency response curves of acoustic regions to theoretical curves of known scattering models. Using the five frequencies on the EK60 system (18, 38, 70, 120, and 200 kHz), three categories of scatterers were defined: fish-like (with swim bladder), nekton-like (e.g., euphausiids), and plankton-like (e.g., copepods). I also employed a multi-frequency acoustic categorization method using three frequencies (18, 38, and 120 kHz) that has been used in the Gulf of Maine and Georges Bank which is based the presence or absence of volume backscatter above a threshold. This method is more objective than the comparison of frequency response curves because it uses an established backscatter value for the threshold. By removing all data below the threshold, only strong scattering information is retained.

In Chapter Three I analyze the distribution of the categorized acoustic regions of interest during the daytime cross shelf transects. Over all transects, plankton-like acoustic regions of interest were detected most frequently, followed by fish-like acoustic regions and then nekton-like acoustic regions. Plankton-like detections were the only significantly different acoustic detections per kilometer, although nekton-like detections were only slightly not significant. Using the threshold categorization method by Jech and Michaels (2006) provides a more conservative and discrete detection of acoustic scatterers and allows me to retrieve backscatter values along transects in areas that have been categorized. This provides continuous data values that can be integrated at discrete spatial increments for wavelet analysis. Wavelet analysis indicates significant spatial scales of interest for fish-like and nekton-like acoustic backscatter range from one to four kilometers and vary among transects.

In Chapter Four I analyze the fine scale distribution of cetaceans in the shelf break system of the Mid-Atlantic Bight using corrected sightings per trackline region, classification trees, multidimensional scaling, and random forest analysis. I describe habitat for common dolphins, Risso’s dolphins and sperm whales. From the distribution of cetacean sightings, patterns of habitat start to emerge: within the shelf break region of the Mid-Atlantic Bight, common dolphins were sighted more prevalently over the shelf while sperm whales were more frequently found in the deep waters offshore and Risso’s dolphins were most prevalent at the shelf break. Multidimensional scaling presents clear environmental separation among common dolphins and Risso’s dolphins and sperm whales. The sperm whale random forest habitat model had the lowest misclassification error (0.30) and the Risso’s dolphin random forest habitat model had the greatest misclassification error (0.37). Shallow water depth (less than 148 meters) was the primary variable selected in the classification model for common dolphin habitat. Distance to surface density fronts and surface temperature fronts were the primary variables selected in the classification models to describe Risso’s dolphin habitat and sperm whale habitat respectively. When mapped back into geographic space, these three cetacean species occupy different fine-scale habitats within the dynamic Mid-Atlantic Bight shelf break system.

In Chapter Five I present a summary of the previous chapters and present potential analytical steps to address ecological questions pertaining the dynamic shelf break region. Taken together, the results of my dissertation demonstrate the use of opportunistically collected data in ecosystem studies; emphasize the need to incorporate middle trophic level data and oceanographic features into cetacean habitat models; and emphasize the importance of developing more mechanistic understanding of dynamic ecosystems.