Rosette Formations on Acid-Etched Titanium

Undergraduate Basi

Evolutionary Robotics: a new scientific tool for studying cognition

We survey developments in Artificial Neural Networks, in Behaviour-based Robotics and Evolutionary Algorithms that set the stage for Evolutionary Robotics in the 1990s. We examine the motivations for using ER as a scientific tool for studying minimal models of cognition, with the advantage of being capable of generating integrated sensorimotor systems with minimal (or controllable) prejudices. These systems must act as a whole in close coupling with their environments which is an essential aspect of real cognition that is often either bypassed or modelled poorly in other disciplines. We demonstrate with three example studies: homeostasis under visual inversion; the origins of learning; and the ontogenetic acquisition of entrainment

Simulating Dynamic Failure of Polymer-Bonded Explosives under Periodic Excitation

Accidental mishandling of explosive materials leads to thousands of injuries in the US every year. Understanding the mechanisms behind the detonation process is crucial to prevent such accidents. In polymer-bonded explosives (PBX), high-frequency mechanical excitation generates thermal energy and can lead to an increase in temperature and vapor pressure, and potentially the initiation of the detonation process. However, the mechanisms behind this energy release, such as the effects of dynamic fracture and friction, are not well understood. Experimental data is difficult to collect due to the different time scales of reactions and vibrations, so research is aided by running simulations to computationally understand experimental results. Using phase-field model of fracture, we simulate the behaviors of various crack orientations in single particles of HMX bonded in a polymer matrix. Larger amplitudes induce higher rates of energy buildup which lead to quicker crack propagation, while higher frequencies generate higher spikes in temperature. However, crack location and orientation with respect to loading also significantly affect damage rates and temperature fluctuations. Cracks perpendicular to the loading vibration wave propagate most readily and appear to generate the most frictional energy, especially along the crystal-polymer interface

Regulation of chemokine receptor expression and function on CD4+T lymphocytes during central nervous system inflammation.

Chemokines are a family of cytokines that exhibit selective chemoattractant properties for target leukocytes, including CD4⁺ T lymphocytes, and play a significant role leukocyte migration. However, a target leukocyte can only respond to a chemokine if it expresses the cognate receptor(s). Recent studies have demonstrated alterations in both chemokine and chemokine receptor expression patterns in the CNS during experimental autoimmune encephalomyelitis (EAE), a model for Multiple Sclerosis. Accordingly, the aim of the research presented in this thesis was to investigate chemokine receptor regulation and function on CD4⁺ T lymphocytes during T cell-mediated central nervous system (CNS) inflammation in vivo. In the proteolipid protein (PLP)-induced model of EAE, two inflammatory (CXCR3 and CCR5) and one supposedly homeostatic (CXCR4) chemokine receptors were up regulated on CD4⁺ T cells during antigen-dependent clonal selection in the draining lymph nodes. As the CD4⁺ T cells migrated through the blood and into the CNS tissue, expression of these receptors remained elevated such that, at the peak of clinical disease, the majority of neuroantigen-specific CD4⁺ T cells in the CNS expressed elevated levels of CXCR4, CXCR3 and CCR5. Detailed characterisation of these receptors revealed that upregulation occurred in co-ordination with cellular division. Subsequent experiments were performed in order to determine the biological consequences of specific chemokine/receptor interactions during EAE. Amino terminal modifications of chemokines, which convert agonists to antagonists, have previously been shown to interfere with ligand/receptor interactions during inflammation. Therefore, a series of synthetic N-terminal chemokine mutants were initially tested in vitro for their ability to act as antagonists in preventing the migration of neuroantigen-activated lymphocytes to ligands of the receptors CXCR4, CXCR3 and CCR5. These analyses revealed that the synthetic mutants SDF-1 P2G, I-TAC 4-79 and RANTES 9-68 possessed potent antagonistic capacities. Following EAE induction, treatment every second day with the antagonists until day 15 resulted in a significant decrease in the severity of the neurological symptoms of EAE. Histological analyses demonstrated that the reduction in disease severity corresponded with a reduced number of inflammatory infiltrates in the spinal cords of antagonist-treated mice at peak clinical disease compared with control-treated mice. The ability to separate the disease process into two separate phases (sensitisation and effector) using adoptive transfer experiments provided a means to investigate the temporal and spatial control that specific chemokine/receptor interactions exerted during the pathogenesis of EAE. Accordingly, a series of ex vivo proliferation assays and adoptive transfer experiments were conducted. From these experiments, a potential role for the SDF-1/CXCR4 interaction was identified in the sensistisation phase of the disease. These results indicated that SDF-1/CXCL12 and CXCR4 interactions not only play a role in homeostasis, but may also provide costimulatory signals to antigen-stimulated CD4⁺ T cells. Converely, roles for I-TAC/CXCR3 and RANTES/CCR5 interactions, but not SDF-1/CXCR4 interactions were identified in the effector phase of EAE. Collectively, the results generated in the present thesis, together with those from other studies, enabled the construction of a model detailing the temporal and spatial parameters of chemokine/chemokine receptor regulation of CD4⁺ T cell activation and migration during a CD4⁺ T cell-mediated immune response in the CNS.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 200

The Effects of Negative Economic Shocks at Birth on Adolescents’ Cognitive Health and Educational Attainment in Malawi

We provide new evidence of the association between moderate negative economic shocks in utero or shortly after birth and adolescents’ cognitive outcomes and educational attainment in Malawi. This is one of the first studies to analyze the effect of not one, but multiple moderate negative economic shocks in a sub-Saharan African (SSA) low-income country (LIC). This focus is important as multiple economic shocks in early life are more representative of the experiences of adolescents in LICs. Combining data on adolescents aged 10-16 from the Adverse Childhood Experiences (ACE) project with the Malawi Longitudinal Study on Families and Health (MLSFH) (N = 1; 559), we use linear and probit regression models to show that girls whose households experienced two or more economic shocks in their year of birth have lower cognitive skills as measured by working memory, reading and mathematical skills. Girls also have lower educational attainment, conditional on age. These effects are gendered, as we do not observe similar effects among boys. Overall, our results point to lasting effects of early-life adversity on adolescents, and they highlight that, even in a LIC context where early-life adversity is common, policymakers need to intervene early to alleviate the potential long-term educational impacts of in utero or early life shocks among girls

Morphological and mechanical characterization of bone phenotypes in the Amish G610C murine model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a hereditary bone disease where gene mutations affect Type I collagen formation resulting in osteopenia and increased fracture risk. There are several established mouse models of OI, but some are severe and result in spontaneous fractures or early animal death. The Amish Col1a2G610C/+ (G610C) mouse model is a newer, moderate OI model that is currently being used in a variety of intervention studies, with differing background strains, sexes, ages, and bone endpoints. This study is a comprehensive mechanical and architectural characterization of bone in G610C mice bred on a C57BL/6 inbred strain and will provide a baseline for future treatment studies. Male and female wild-type (WT) and G610C mice were euthanized at 10 and 16 weeks (n = 13-16). Harvested tibiae, femora, and L4 vertebrae were scanned via micro-computed tomography and analyzed for cortical and trabecular architectural properties. Femora and tibiae were then mechanically tested to failure. G610C mice had less bone but more highly mineralized cortical and trabecular tissue than their sex- and age-matched WT counterparts, with cortical cross-sectional area, thickness, and mineral density, and trabecular bone volume, mineral density, spacing, and number all differing significantly as a function of genotype (2 Way ANOVA with main effects of sex and genotype at each age). In addition, mechanical yield force, ultimate force, displacement, strain, and toughness were all significantly lower in G610C vs. WT, highlighting a brittle phenotype. This characterization demonstrates that despite being a moderate OI model, the Amish G610C mouse model maintains a distinctly brittle phenotype and is well-suited for use in future intervention studies

Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter

In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (∼100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use

Yeast:One cell, one reference sequence, many genomes?

The genome of Saccharomyces cerevisiae – brewer’s or baker’s yeast – was the first eukaryotic genome to be sequenced in 1996. The identity of that yeast genome has been not just a product of sequencing, but also of its use after sequencing and particularly of its mobilization in scientific literature. We ask “what is the yeast genome?” as an empirical question by investigating “the yeast genome” as a discursive entity. Analyzing publications that followed sequencing points to several “yeast genomes” existing side-by-side: genomes as physical molecules, digital texts, and a historic event. Resolving this unified-yet-multiple “genome” helps make sense of contemporary developments in yeast genomics such as the synthetic yeast project, in which apparently “the same” genome occupies multiple roles and locations, and points to the utility of examining specific non-human genomes independent of the Human Genome Project

The Effect of Single Versus Group μCT on the Detection of Trabecular and Cortical Disease Phenotypes in Mouse Bones

Micro‐computed tomography is a critical assessment tool for bone‐related preclinical research, especially in murine models. To expedite the scanning process, researchers often image multiple bones simultaneously; however, it is unknown if this impacts scan quality and alters the ability to detect differences between experimental groups. The purpose of this study was to assess the effect of multibone scanning on detecting disease‐induced changes in bone microarchitecture and mineral density by group scanning two murine models with known skeletal defects: the Col1a2 G610C/+ model of osteogenesis imperfecta and an adenine‐induced model of chronic kidney disease. Adult male femurs were scanned individually and in random groups of three and eight in a Bruker Skyscan 1172 and 1176, respectively, then assessed for standard trabecular and cortical bone measures. Although scanning methodology altered raw values, with trabecular microarchitecture values more affected than cortical properties, a disease phenotype was still detectable in both group and solo scans. However, tissue mineral density in both trabecular and cortical bone was significantly impacted by group versus solo scanning. Researchers may be able to use small groupings in a single μCT scan to expedite preclinical analyses when the overall bone phenotype is large to decrease costs and increase speed of discoveries; however the details of scanning (single or group) should always be reported