Investigating the role of HDAC4 in Drosophila neuronal function : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in Genetics at Massey University, Manawatū, New Zealand

Figures 1.12 & 6.11 were re-used with the respective publisher's permission.HDAC4 plays an essential role in brain functions including neurodevelopment and memory formation, and increased levels of HDAC4 have also been associated with neurodegenerative disorders including Alzheimer’s disease. Histone deacetylases are enzymes that are traditionally known to regulate gene expression in the nucleus, however in neurons, HDAC4 shuttles between the nucleus and cytoplasm with a predominant distribution in the cytoplasm. Although studies have identified potential differences in subcellular function in which accumulation of nuclear HDAC4 has been shown to promote neurodegeneration, while cytoplasmic HDAC4 is neuroprotective, the mechanistic pathways through which it acts are still unknown. Therefore, this project aimed to determine the importance of nuclear and cytoplasmic pools of HDAC4 to the neurological functions of Drosophila melanogaster, as well as to determine the domains within the protein that are required for its function(s). This was carried out by expressing HDAC4 with mutations that resulted in altered subcellular distribution or carrying mutations in binding domain/motifs that have previously been shown to be important for HDAC4 function. Increased expression of wild-type HDAC4 disrupted development of the retina and the mushroom body (MB, a brain structure derived from Kenyon cells which are crucial for learning and memory), and expression of each mutant revealed the importance of specific domains/motifs to HDAC4 function in these tissues. Of interest, impairments to MB formation were exacerbated by mutation of the ankyrin-binding site and by mutation of serine residues that promote nuclear exit when phosphorylated (i.e. resulting in restriction to the nucleus). Mutation of the MEF2-binding site ameliorated these phenotypes, suggesting that HDAC4 acts through MEF2 to regulate MB development. However, while deacetylase activity was found to be dispensable in the MB, an active deacetylase domain was required in order for the phenotype to manifest in the retina, and mutation of the MEF2-binding site had no impact on the deficits caused by nuclear restriction of HDAC4 and mutation of the ankyrin-binding domain. Together these data indicate that HDAC4 acts through varying mechanism(s) depending on the cell type. Transcriptional changes in the Drosophila brain resulting from the expression of HDAC4 or its mutant variants was also explored using RNA-Seq. However only wild-type HDAC4 resulted in a large number of differentially expressed genes and the low level of differential gene expression in HDAC4 variants suggests that non-transcriptional processes may be involved in the induction of phenotypes caused by expression of these mutants. Additionally, further analysis of genes that were differentially regulated revealed a number of processes related to mitochondrial energy production. These findings have provided new insights into the role of HDAC4 in Drosophila neurodevelopment which opens up additional research avenues to focus on in the future

Multi-disciplinary investigation of a flap blown turboelectric distributed propulsion blended wing body aircraft.

Growing concerns about the rising costs of fuel as well as environmental issues have led to multiple innovative and futuristic aircraft concepts to tackle these issues. Turboelectric Distributed Propulsion (TeDP) and boundary layer ingestion are two such concepts. When applied to a conceptual aircraft such as the N3-X, it results in a blended wing body (BWB) aircraft with an array of fan propulsors mounted near the rear of the aircraft body and driven by superconducting motors powered by superconducting generators in the wing tip mounted turbogenerators. The elevator flaps of such a BWB aircraft are located at the trailing edge of the aircraft body. Coupled with the exhaust mass flow from the propulsor fan nozzles, it presents a chance to utilize flap blowing and/or thrust vectoring to further improve on the aircraft performance. By utilizing boundary layer ingestion, there can be expected 5-6% total fuel savings while flap blowing can further enhance the fuel savings to a total of 8-9%. However, integration issues such as intake pressure losses, deficiency in fan propulsor efficiency tends to mitigate the benefits derived. Furthermore, it is difficult to separate various design disciplines such as aerodynamics and propulsion in such a high integrated aircraft. Flap blowing further correlates to both disciplines. This dissertation addresses a broad overall design methodology that is both multi-disciplinary and multi-fidelity, addressing the above mentioned issues. Flap blowing can be seen to be a linkage between the often separate aerodynamics and propulsion design disciplines in an aircraft. The strip method code, designed to incorporate flap blowing into the preliminary design and analysis is presented in this study, showing its impact on aerodynamic performance, flight dynamic response and propulsion system design. Furthermore, other disciplines such as boundary layer ingestion, weight, and flight dynamics are considered and incorporated into the methodology. The main figure of merit used is the total fuel consumption of the aircraft and in addition, take-off distances are also studied and analysed. Take-off distances incorporating flap blowing and thrust vectoring demonstrated a reduction in distances between 25-30%. The reduction in take-off distance also led to the study on the potential of re-sizing the BWB outer wings to further reduce total fuel consumption and has shown great promise.PhD in Aerospac

Polytypism and Unexpected Strong Interlayer Coupling of two-Dimensional Layered ReS2

The anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and potential application, have one more dimension to tune the properties than the isotropic 2D materials. The interlayer vdW coupling determines the properties of 2D multi-layer materials by varying stacking orders. As an important representative anisotropic 2D materials, multilayer rhenium disulfide (ReS2) was expected to be random stacking and lack of interlayer coupling. Here, we demonstrate two stable stacking orders (aa and a-b) of N layer (NL, N>1) ReS2 from ultralow-frequency and high-frequency Raman spectroscopy, photoluminescence spectroscopy and first-principles density functional theory calculation. Two interlayer shear modes are observed in aa-stacked NL-ReS2 while only one interlayer shear mode appears in a-b-stacked NL-ReS2, suggesting anisotropic-like and isotropic-like stacking orders in aa- and a-b-stacked NL-ReS2, respectively. The frequency of the interlayer shear and breathing modes reveals unexpected strong interlayer coupling in aa- and a-b-NL-ReS2, the force constants of which are 55-90% to those of multilayer MoS2. The observation of strong interlayer coupling and polytypism in multi-layer ReS2 stimulate future studies on the structure, electronic and optical properties of other 2D anisotropic materials

An evolutionary algorithm with double-level archives for multiobjective optimization

Existing multiobjective evolutionary algorithms (MOEAs) tackle a multiobjective problem either as a whole or as several decomposed single-objective sub-problems. Though the problem decomposition approach generally converges faster through optimizing all the sub-problems simultaneously, there are two issues not fully addressed, i.e., distribution of solutions often depends on a priori problem decomposition, and the lack of population diversity among sub-problems. In this paper, a MOEA with double-level archives is developed. The algorithm takes advantages of both the multiobjective-problemlevel and the sub-problem-level approaches by introducing two types of archives, i.e., the global archive and the sub-archive. In each generation, self-reproduction with the global archive and cross-reproduction between the global archive and sub-archives both breed new individuals. The global archive and sub-archives communicate through cross-reproduction, and are updated using the reproduced individuals. Such a framework thus retains fast convergence, and at the same time handles solution distribution along Pareto front (PF) with scalability. To test the performance of the proposed algorithm, experiments are conducted on both the widely used benchmarks and a set of truly disconnected problems. The results verify that, compared with state-of-the-art MOEAs, the proposed algorithm offers competitive advantages in distance to the PF, solution coverage, and search speed

Collaborative MR Workspace with Shared 3D Vision Based on Stereo Video Transmission

P.R.China Mixed reality (MR) research aims to develop technologies that inputting or mixing the rea

Adsorption Properties of Copper (II) Ion From Aqueous Solution by Starch-Grafted Polyacrylamide and Crosslinked Starch-Grafted Polyacrylamide

Starch-grafted polyacrylamide (SA) and cross-linked starch-grafted polyacrylamide (CSA) had been synthesized via grafting polymerization from corn starch and used as adsorbents for the removal of Cu(II) ion from aqueous solution. The equilibrium, kinetics and thermodynamics of adsorption processes of SA and CSA were investigated and compared. It was found that the adsorption capacity of Cu(II) of SA and CSA could reach the maximum within 60 min when the pH was 6. The adsorption kinetics of CSA and SA for Cu(II) was favorably described by the pseudo-second-order kinetic model and the adsorption isotherm was described well with the Freundlich isotherm model. Thermodynamic studies indicated that the adsorption was a spontaneous and endothermic process with increased entropy, and the rise of temperature would benefit the adsorption; the enthalpy change(ΔH), the entropy change (ΔS) and free energy change (ΔG) of the adsorption process of Cu(II) on SA and CSA were calculated with adsorption isotherm data and basic thermodynamic relations

Optimizing Survivorship Care Services for Asian Adolescent and Young Adult Cancer Survivors: A Qualitative Study.

Purpose: With an increasing focus on developing survivorship services tailored for adolescent and young adult (AYA) cancer survivors, incorporation of viewpoints from both survivors and health care professionals (HCPs) is important. This study aims to explore the perceptions of current and prospective survivorship services from both groups in Singapore to propose service design and delivery strategies. Methods: Focus group discussions with 23 AYA cancer survivors between the ages of 16 and 39 years at diagnosis and 18 HCPs were conducted in National Cancer Centre Singapore (NCCS) and Singapore Cancer Society (SCS). All focus group discussions were transcribed verbatim. Deductive thematic analysis was performed according to the components of a design thinking model: empathizing with AYA survivors, defining care gaps, proposing services, and implementation strategies. Results: AYA survivors preferred age-specific services that are aligned with their personal goals. Current survivorship care failed to address the needs of survivors' dependents (caregivers and children) and to consider the utility of each service temporally. Prospective services should clarify disease disclosure obligation in job search and introduce a care navigator. Key implementation strategies included (1) training HCPs on communication techniques with AYA, (2) selecting engagement platforms that complement survivors' information-seeking behavior, (3) improving outreach to survivors through appropriate branding and publicity, and (4) consolidating services from multiple providers. Conclusions: The design of survivorship care services for AYA survivors should be systematic in its conceptualization process and employ implementation strategies. The coordination of the wide spectrum of services warrants a concerted effort by cancer centers, community partners, and the government