Evolution of the gene regulatory network controlling trunk segmentation in insects

The study of pattern formation in insects is the main source of our current understanding of the genetic processes underlying the development of an organism. Ontogeny has been thoroughly studied in the model organism Drosophila melanogaster, where a set of transcription factors and signaling molecules pattern the fly embryo through a segmentation gene cascade. Over the past 20 years, this model has been compared to different organisms throughout the Metazoa. Here I describe the functional analysis of genes and gene regulatory network controlling segmentation in the short germ beetle Tribolium castaneum. The hunchback gene is one of the major early determinants in the Drosophila segmentation cascade, where it serves an instructive role in patterning the entire body plan. In several insects, the role of hb in patterning body compartments (cardinal regions) is conserved. However, in hemimetabolous insects developing as short germs hb role has been reported to differ from the canonical gap function described in holometabolous insects. In the first chapter I describe the role of hb in Tribolium, a holometabolous insect developing as short germ. This analysis revealed that Tc'hb has an indirect effect in segmentation, mediated by other gap genes like giant, and a most likely a direct effect in the segment identity specification, by setting the anterior border of thoracic and abdominal Hox genes. This finding suggests an ancestral role of hb as a cardinal gene within insects and allows the reinterpretation of the canonical gap phenotype described in the fly. The expression analysis of ESTs in Tribolium identified a putative non-coding RNA showing a gap-like expression pattern during segmentation. In the second chapter I describe the functional analysis of this gene, named mille-pattes. This analysis defined Tc'mlpt as a novel segmentation gene in Tribolium, which controlls trunk segmentation in a cross-regulatory network among gap genes and regulates the expression domains of Hox genes. Strikingly, mlpt does not code for a transcription factor, but instead, encodes several small peptides, which are conserved among mlpt homologues in various insects. As a model, the gene regulatory network controlling segmentation in Drosophila has been thoroughly tested in many other organisms, revealing a surprising plasticity of the developmental mechanism controlling segmentation among insects. In order to identify the regulatory interactions among the gap genes that are controlling segmentation in Tribolium, I further characterized the gap gene cross-regulatory network in Tribolium and their interaction with pair rule genes. This analysis provided a powerful data set on the regulatory interactions among gap genes and their interactions with pair rule genes in Tribolium. Finally, the concomitant characterization of segmentation genes presented in this thesis allowed the reinterpretation of the role of hunchback among insects, specially the canonical gap phenotype described for Tribolium and Drosophila. Furthermore, by studying the interactions between gap and Hox genes in Tribolium it was possible to propose a model for the regulation and function of Tc'Antp and for the regulation of the Hox genes along the AP axis in Tribolium

Analysis of pattern dynamics for a nonlinear model of the human cortex via bifurcation theories

This thesis examines the bifurcations, i.e., the emergent behaviours, for the Waikato cortical model under the influence of the gap-junction inhibitory diffusion D₂ (identified as the Turing bifurcation parameter) and the time-to-peak for hyperpolarising GABA response γi (i.e., inhibitory rate-constant, identified as the Hopf bifurcation parameter). The cortical model simplifies the entire cortex to a cylindrical macrocolumn (∼ 1 mm³) containing ∼ 10⁵ neurons (85% excitatory, 15% inhibitory) communicating via both chemical and electrical (gap-junction) synapses. The linear stability analysis of the model equations predict the emergence of a Turing instability (in which separated areas of the cortex become activated) when gap-junction diffusivity is increased above a critical level. In addition, a Hopf bifurcation (oscillation) occurs when the inhibitory rate-constant is sufficiently small. Nonlinear interaction between these instabilities leads to spontaneous cortical patterns of neuronal activities evolving in space and time. Such model dynamics of delicately balanced interplay between Turing and Hopf instabilities may be of direct relevance to clinically observed brain dynamics such as epileptic seizure EEG spikes, deep-sleep slow-wave oscillations and cognitive gamma-waves. The relationship between the modelled brain patterns and model equations can normally be inferred from the eigenvalue dispersion curve, i.e., linear stability analysis. Sometimes we experienced mismatches between the linear stability analysis and the formed cortical patterns, which hampers us in identifying the type of instability corresponding to the emergent patterns. In this thesis, I investigate the pattern-forming mechanism of the Waikato cortical model to better understand the model nonlinearities. I first study the pattern dynamics via analysis of a simple pattern-forming system, the Brusselator model, which has a similar model structure and bifurcation phenomena as the cortical model. I apply both linear and nonlinear perturbation methods to analyse the near-bifurcation behaviour of the Brusselator in order to precisely capture the dominant mode that contributes the most to the final formed-patterns. My nonlinear analysis of the Brusselator model yields Ginzburg-Landau type amplitude equations that describe the dynamics of the most unstable mode, i.e., the dominant mode, in the vicinity of a bifurcation point. The amplitude equations at a Turing point unfold three characteristic spatial structures: honeycomb Hπ, stripes, and reentrant honeycomb H₀. A codimension-2 Turing–Hopf point (CTHP) predicts three mixed instabilities: stable Turing–Hopf (TH), chaotic TH, and bistable TH. The amplitude equations precisely determine the bifurcation conditions for these instabilities and explain the pattern-competition mechanism once the bifurcation parameters cross the thresholds, whilst driving the system into a nonlinear region where the linear stability analysis may not be applicable. Then, I apply the bifurcation theories to the cortical model for its pattern predictions. Analogous to the Brusselator model, I find cortical Turing pattens in Hπ, stripes and H₀ spatial structures. Moreover, I develop the amplitude equations for the cortical model, with which I derive the envelope frequency for the beating-waves of a stable TH mode; and propose ideas regarding emergence of the cortical chaotic mode. Apart from these pattern dynamics that the cortical model shares with the Brusselator system, the cortical model also exhibits “eye-blinking” TH patterns latticed in hexagons with localised oscillations. Although we have not found biological significance of these model pattens, the developed bifurcation theories and investigated pattern-forming mechanism may enrich our modelling strategies and help us to further improve model performance. In the last chapter of this thesis, I introduce a Turing–Hopf mechanism for the anaesthetic slow-waves, and predict a coherence drop of such slow-waves with the induction of propofol anaesthesia. To test this hypothesis, I developed an EEG coherence analysing algorithm, EEG coherence, to automatically examine the clinical EEG recordings across multiple subjects. The result shows significantly decreased coherence along the fronto-occipital axis, and increased coherence along the left- and right-temporal axis. As the Waikato cortical model is spatially homogenous, i.e., there are no explicit front-to-back or right-to-left directions, it is unable to produce different coherence changes for different regions. It appears that the Waikato cortical model best represents the cortical dynamics in the frontal region. The theory of pattern dynamics suggests that a mode transition from wave–Turing–wave to Turing–wave–Turing introduces pattern coherence changes in both positive and negative directions. Thus, a further modelling improvement may be the introduction of a cortical bistable mode where Turing and wave coexist

Bit-parallel and SIMD alignment algorithms for biological sequence analysis

High-throughput next-generation sequencing techniques have hugely decreased the cost and increased the speed of sequencing, resulting in an explosion of sequencing data. This motivates the development of high-efficiency sequence alignment algorithms. In this thesis, I present multiple bit-parallel and Single Instruction Multiple Data (SIMD) algorithms that greatly accelerate the processing of biological sequences. The first chapter describes the BitPAl bit-parallel algorithms for global alignment with general integer scoring, which assigns integer weights for match, mismatch, and insertion/deletion. The bit-parallel approach represents individual cells in an alignment scoring matrix as bits in computer words and emulates the calculation of scores by a series of logic operations. Bit-parallelism has previously been applied to other pattern matching problems, producing fast algorithms. In timed tests, we show that BitPAl runs 7 - 25 times faster than a standard iterative algorithm. The second part involves two approaches to alignment with substitution scoring, which assigns a potentially different substitution weight to every pair of alphabet characters, better representing the relative rates of different mutations. The first approach extends the existing BitPAl method. The second approach is a new SIMD algorithm that uses partial sums of adjacent score differences. I present a simple partial sum method as well as one that uses parallel scan for additional acceleration. Results demonstrate that these algorithms are significantly faster than existing SIMD dynamic programming algorithms. Finally, I describe two extensions to the partial sums algorithm. The first adds support for affine gap penalty scoring. Affine gap scoring represents the biological likelihood that it is more likely for gaps to be continuous than to be distributed throughout a region by introducing a gap opening penalty and a gap extension penalty. The second extension is an algorithm that uses the partial sums method to calculate the tandem alignment of a pattern against a text sequence using a single pattern copy. Next generation sequencing data provides a wealth of information to researchers. Extracting that information in a timely manner increases the utility and practicality of sequence analysis algorithms. This thesis presents a family of algorithms which provide alignment scores in less time than previous algorithms

Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation

Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the “pair-rule” genes, are still not well understood at the system level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic “gap” inputs. This result suggests that dynamic shifts of pair-rule stripes are essential for segment patterning in the trunk, and provides a functional role for observed posterior-to-anterior gap domain shifts that occur during cellularisation. The model also suggests revised patterning mechanisms for the parasegment boundaries, and explains the aetiology of the even-skipped null mutant phenotype. Strikingly, a slightly modified version of the model is able to pattern segments in either simultaneous or sequential modes, depending only on initial conditions. This suggests that fundamentally similar mechanisms may underlie segmentation in short-germ and long-germ arthropods.Isaac Newton Trust www.newtontrust.cam.ac.uk. Research grant. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Biotechnology and Biological Sciences Research Council www.bbsrc.ac.uk. Genes to Organisms PhD studentship. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Fracture Resistance and Microleakage around Direct Restorations in High C-Factor Cavities

The aim of this research was to evaluate the mechanical impact of different direct restorations in terms of fracture resistance, and subsequent fracture pattern, in occlusal high C-factor cavities. Furthermore, the adaptation of different direct restorations in the form of gap formation was also evaluated. Seventy-two intact mandibular molars were collected and randomly distributed into three groups (n = 24). Class I occlusal cavities with standardized dimensions were prepared in all specimens. After adhesive treatment, the cavities were restored with direct restorations utilizing three different materials. Group 1: layered conventional packable resin composite (Filtek Ultimate), Group 2: bulk-fill resin composite (SDR), Group 3: bulk-fill short fibre-reinforced composite (SFRC; everX Posterior) covered with packable composite occlusally. Half of the restored specimens underwent static load-to fracture testing (n = 12/group), while the rest underwent sectioning and staining for microleakage evaluation and gap formation analysis. Fracture patterns were evaluated visually among the mechanically tested specimens. The layered composite restoration (Group 1) showed significantly lower fracture resistance compared to the bulk fill groups (Group 2, p = 0.005, Group 3, p = 0.008), while there was no difference in fracture resistance between the other groups. In terms of gap formation values, the layered composite restoration (Group 1) produced significantly higher gap formation compared to the bulk-fill groups (Group 2, p = 0.000, Group 3, p = 0.000). Regarding the fracture pattern, SFRC (Group 3) produced the highest number, while SDR (Group 2) produced the lowest number of repairable fractures. The use of bulk-fill resin composite (fibre or non-fibre-reinforced) for occlusal direct restorations in high C-factor cavities showed promising achievements regarding both fracture resistance and microleakage. Furthermore, the use of short fibre-reinforced bulk-fill composite can also improve the fracture pattern of the restoration-tooth unit. Bulk-fill materials provide a simple and effective solution for restoring and reinforcing high C-factor occlusal cavities

Ground Reaction And Behaviour Of Tunnels In Soft Clays

A consistent, systematic approach for predicting settlements above tunnels in soft clay is presented. This predictive scheme provides firstly, a simple method for calculating the maximum surface settlement, and secondly, a detailed method for determining the overall pattern of displacements. In the simple method, the maximum surface settlement is estimated from its relationship with the crown displacement which can be calculated theoretically. The detailed method requires finite element analysis and comprehensive field and laboratory testing. Since the detailed analysis may be used for predicting subsurface as well as surface displacements, it is considered to be very useful for analyzing critical sections of a tunnel. The development of this technique is described and its validity and applicability are examined.;Settlement due to tunnelling is generally attributed to loss of ground and volume change in soil. In this thesis, a gap parameter is used to quantify ground loss and to model approximately the effect of soil reconsolidation in the remoulded area above the crown. The components of the gap parameter are (i) the three-dimensional elasto-plastic deformation at the advancing face of the tunnel, (ii) the physical gap defined by the shield-lining geometry, (iii) the displacement associated with workmanship which includes the effect of grouting. An additional component due to consolidation of remoulded soil above the crown may be included as part of the gap where appropriate. The practicality of using this parameter derives from its simplicity in calculation and only conventional soil parameters are required. Comparison of the calculated gap with available field observations showed reasonable agreement. From a study of thirteen case records, an empirical relationship is established for predicting surface settlement from the gap parameter.;A method of detailed analysis using the finite element method is presented. This analysis which is used in conjunction with the concept of the gap parameter, adopts an anisotropic elastic-perfectly plastic model for soil behaviour. The analysis is also formulated to permit consideration of the construction procedure, soil-liner interaction and variation of soil properties with depth.;An extensive field and laboratory investigation of the Thunder Bay soil is performed. The stratigraphy of the instrumented arrays to be examined is well defined. It is shown that the consideration of the appropriate soil stress path is essential in the selection of soil parameters for use in the analysis. . . . (Author\u27s abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UM

Rural and urban disparities in anemia among Peruvian children aged 6-59 months: a multivariate decomposition and spatial analysis

Introduction: Anemia is a global public health issue that affects mainly children aged less than 5 years. In Peru, despite the reduction in the prevalence of anemia between 2010 and 2018, anemia remains a major concern, especially in high-risk zones such as rural areas. Several sociodemographic factors have been associated with anemia in children; however, components contributing to the urban–rural gap have not been previously assessed. The purpose of this study was to evaluate the determinants of the difference in anemia prevalence between urban and rural areas, and its spatial distribution in Peruvian children aged 6–59 months. Methods: A secondary data analysis was conducted using the 2019 Peruvian Demographic Health Survey. The study population included 18 846 children aged 6–59 months. A multivariate decomposition analysis for non-linear response model was performed to identify the factors contributing to the gap in the prevalence of anemia across urban and rural areas. Global Moran's I autocorrelation, Ordinary Kriging interpolation and Bernoullibased purely spatial scan statistics were employed to assess the spatial pattern of anemia. Results: Nationwide, the prevalence of anemia in Peru was 29.47% (95%CI 28.63–30.33). In rural areas, it was 38.25%, and in urban areas 26.39%. The decomposition analysis revealed that 88.61% of the difference in the prevalence of anemia between urban and rural areas was attributed to the difference in the respondents’ characteristics. Wealth index, mother's education, mother's employment status, number of living children and mother's age were key determinants contributing to the rural–urban gap. Spatial heterogeneity of anemia prevalence in childhood was observed at both inter and intradepartmental level. The SaTScan spatial analysis identified six significant cluster areas with high prevalence of anemia in childhood. Conclusion: A considerable gap of anemia prevalence between urban and rural areas was found. Targeted interventions are necessary to reduce geographic disparities.Revisión por pare

A Case Study of the Perspectives of Black Children\u27s Parents Regarding Their Role in Addressing the Achievement Gap

The purpose of this qualitative, collective case study was to understand the perspectives of Black children\u27s parents regarding their roles in addressing the Black student achievement gap in their Virginia school district. For this study, the achievement gap referred to the disparity of academic performance between Black and White students. The theories guiding this study were social constructivism and social equity as they both support understanding the world based on participants’ experiences. The research questions are as follows: (1) What do parents of Black children identify as their roles in their children’s education? (2) How do parents of Black children perceive the effect that their involvement has on their children\u27s academic success or failure? (3) What additional support do parents of Black children need to facilitate better learning for their children? This study was bound to a Virginia school district, and the sample was composed of 12 participants from 2 schools: Harris Middle School and Sims High School. The data collection process included individual interviews, a focus group, and a historical document analysis provided by the school. Data analysis was conducted using pattern matching logic and consisted of coding, memoing, and transcripts interpretation. The study’s findings indicated that parents largely believe that the burden of education lies within the schools. Additionally, parents feel that as their student reaches the end of middle school, the child should be held to higher accountability for their success. By performing this study, I offered a better understanding of Black parents\u27 perception regarding their specific roles in addressing the minority achievement gap

Essays on the Gender Wage Gap in China and the Returns to Higher Education in the United States

This dissertation presents three separate essays. The first two essays explore the gender wage gap and its dynamics in urban China from 1995 to 2018. The first chapter decomposes the gender wage gap based on the observed wage for workers with a precise measure of the hourly wages. The first chapter examines the observed average gender wage gap in China in hourly wages from 1995 to 2018. Using data from the China Household Income Survey (CHIP) 1995 – 2013 and the China Family Panel Studies (CFPS) 2014 and 2018. This chapter computes wage earners\u27 working hours and hourly wages based on the available information to account for the labor supply\u27s intensive margin. This chapter shows a pattern of increase in the gender wage gap in terms of hourly wages in the survey years of 1995-2007 and a pattern of decrease in 2007 - 2013. By extending the study period to 2018, this paper provides additional evidence that the observed wage-earners gender wage differentials have continued to decrease from 2013 - 2018 in urban China. This chapter finds that educational achievement and the returns to education favor female workers on average; however, the returns to potential experience are the main contributors to the ``unexplained component of the gender wage gap. This chapter also finds that the changes in the gender wage gap are heterogeneous across groups. Individuals without a college degree and working in foreign-owned firms are more likely to experience gender wage differential changes in hourly wages compared with those with at least a college degree and working in State-Owned Enterprises(SOEs). The second chapter explores the gender wage gap dynamics by accounting for employment composition. This chapter examines changes in the gender gap of the wage distribution in China from 1995 to 2018. To effectively account for changes in employment composition, we employ nonparametric bounds. Our methodology adopts a weak quartile dominance assumption, a monotone instrumental variable, and a stochastic dominance assumption to tighten the bounds. The results show statistically significant evidence that, over the years from 1995 to 2018, the median gender wage gap for the young workers (age 25-45) who are non-college-educated has increased by 0.17 - 0.62 log points. To estimate potential changes in the evolution of the gender wage gap suggested in the literature, we split up our analysis into two periods from 1995 - 2007 and 2007 - 2018. The results show larger changes in the gender wage gap compared to estimates in existing studies. In the eailer period, we find a significant increase by 0.19 - 0.63 log points in the median gender wage gap among the young workers who are college-educated. In the second period, the bounds estimates are less conclusive and suggest a decrease in the median gender wage gap among the college-educated young workers by 0.12 - 0.59 log points, but their 95\% CI does not exclude a zero change. The estimates of the gender wage gap at the $75^{th}$ wage percentile show a similar pattern as the changes at the median wage, while the statistical implications at the $25^{th}$ percentile are inconclusive. Chapter three examines the returns to higher education in the United States with particular attention to individuals induced by the recession to attend a Master’s Program. Unlucky college undergraduates entering the labor market in a recession suffer a persistent loss in their earnings in the medium- to long-term. Due to this ``scarring effect, the opportunity cost for graduate school attendance decreases when an individual is exposed to a recession. This paper examines whether staying in school can help the unlucky cohort in terms of future labor market outcomes. There are two channels: delaying the time to enter the labor force and human capital accumulation. I find that graduating during a recession increases the probability of pursuing a graduate degree by 3 percentage points, and the return for the induced graduate degree is about 23\% in future annual salary. At the same time, there is no statistically significant effect on the employment probability for those graduate degree holders induced by the recession. These findings provide evidence that the main benefit those induced graduate degree holders gain is from the additional accumulated human capital; the effect of delayed labor force entrance is negligible. I also find younger non-white females in non-STEM majors from non-research universities are more sensitive to the recession when making the graduate school decision

A Principal as Literacy Leader: Promoting Literacy Outcomes for Third-grade Students of Color

Early literacy is the foundation for students’ academic (GPEE, 2019; Murphy, 2004) and future economic success (Carnevale et al., 2013; Frizzell et al., 2017; GPEE, 2019). However, a reading achievement gap continues to exist between low-income children, students of color, and their White and affluent peers (Au, 2007; Fiester, 2013; Hernandez, 2011; Salloum et al., 2017). Because third-grade reading proficiency has been linked to high school graduation (Fiester, 2013), the academic and employment success of students of color is determined by their ability to read. This qualitative, intrinsic case study will examine the literacy leadership practices of a Title I elementary principal in the southeastern United States. Through the lens of instructional leadership for literacy and culturally responsive school leadership for literacy, this study will examine how the principal (1) bolstered the outcomes of third-grade students of color and (2) formed partnerships with the parents and families of third-grade students of color to increase literacy outcomes. Data collection will entail school observations; principal, assistant principal, literacy or instructional coach, media specialist, and parent interviews; a teacher focus group; and document reviews. Data analysis will be conducted through an iterative process of reviewing, pattern-seeking, and regrouping (Stake, 1995). Methodological triangulation, member checking, and iterative questioning will confirm interpretations from the data collection process (Stake, 1995). The findings will report how the principal used literacy leadership practices to close the reading achievement gap for students of color in a Title I school