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This dissertation examines Australian choral music that is influenced by indigenous Aboriginal music and traditions and the Australian landscape. It traces the evolution of choral composition in Australia, from the early nineteenth century through to modern times, and examines the indigenous Aboriginal music and traditions that date back over 50,000 years. The study begins with an overview of the evolution of Australian choral music, including the establishment of university programs, choral societies, professional arts organizations, and choral ensembles. Chapter two examines the music of the indigenous Aboriginal people, and the relationship between the music, the traditions, and the land. The remainder of this dissertation focuses on the works of nine Australian composers, Peter Sculthorpe (1929-2014), Ross Edwards (b. 1943), Stephen Leek (b. 1959), Sarah Hopkins (b. 1958), Iain Grandage (b. 1970), Paul Stanhope (b. 1969), Paul Jarman (b. 1971), Dan Walker (b. 1978), and Joseph Twist (b. 1982). The works of each of these composers are highly influenced by elements of the Australian landscape as well as aspects of Aboriginal culture. The dissertation concludes with a catalogue of the compositions featured in this study, with information including length of work, publisher information, and web addresses for each composer.

Number rhymes can be used in many exciting and different ways to support the early learning goals for mathematics. The rhyme \"five little speckled frogs\" provides the theme for this display, which was set up in Lewisham's professional development center. It provides a range of ideas which would help develop young children's mathematical learning within the foundation stage. (Author/MM)

Discusses the importance of practitioners planning to exploit the motivational potential of the outdoor environment and supporting children's spontaneous learning across all aspects of mathematics. Presents outdoor activities, each of which involves several learning goals across all areas of mathematics. (KHR)

China's accession to the WTO requires a great many specific policy reforms. However, if the best results are to be obtained, it is important that these reforms be implemented as part of a consistent development program, rather than simply by treating them as a recipe. To do this, policy makers must understand the range and nature of the policy changes required by accession, their implications for the economy, and the availability and effects of supporting policies. China and the WTO analyzes the nature of the reforms involved in China's accession to the WTO, assesses their implications for the world economy, and examines the implications for individual households, particularly the poor. Its key objective is to provide the information that will allow policy makers to implement WTO commitments and formulate supporting policies to contribute strongly to economic development and poverty reduction. Individual chapters by leading scholars analyze the nature of the reforms in key areas, such as agriculture, services, intellectual property and safeguards and anti-dumping. These chapters form the building blocks for later chapters which analyze the implications of reform for the economy. The book also includes a series of studies that assess the implications for households, taking into account the social safety net policies applying in China, and the impacts of complementary policies in areas such as labor market reform and investments in human capital. Of interest to policymakers, academe and students studying international trade issues and to practitioners in the area of trade and development, China and the WTO is a valuable addition to the wealth of information provided by the World Bank Trade and Development Series.

Homeostatic antigen presentation by hepatic antigen-presenting cells, which results in tolerogenic T-cell education, could be exploited to induce antigen-specific immunological tolerance. Here we show that antigens modified with polymeric forms of either N -acetylgalactosamine or N- acetylglucosamine target hepatic antigen-presenting cells, increase their antigen presentation and induce antigen-specific tolerance, as indicated by CD4 + and CD8 + T-cell deletion and anergy. These synthetically glycosylated antigens also expanded functional regulatory T cells, which are necessary for the durable suppression of antigen-specific immune responses. In an adoptive-transfer mouse model of type-1 diabetes, treatment with the glycosylated autoantigens prevented T-cell-mediated diabetes, expanded antigen-specific regulatory T cells and resulted in lasting tolerance to a subsequent challenge with activated diabetogenic T cells. Glycosylated autoantigens targeted to hepatic antigen-presenting cells might enable therapies that promote immune tolerance in patients with autoimmune diseases. Glycosylated peptides targeting hepatic antigen-presenting cells induce antigen-specific immune tolerance, preventing T-cell-mediated diabetes in mice.

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition.

Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies.

Objectives Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion‐stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 ‘MF59C.1’ (Seqirus, Parkville, Australia). Methods A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo‐electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. Results In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S‐specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. Conclusion The SARS‐CoV‐2 Sclamp vaccine candidate is compatible with large‐scale commercial manufacture, stable at 2–8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T‐cell responses and provides protection in animal challenge models. We describe preclinical development of a prefusion stabilized spike protein subunit vaccine for SARS‐CoV‐2. Results include structural resolution by cryo‐electron microscopy, mouse immunogenicity and a hamster protection study.

The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5′-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility. Analysis of the FGF14 -SCA27B repeat locus identifies a common 5′-flanking insertion that represents the major allele, is present exclusively on nonpathogenic alleles, enhances repeat stability and increases chromatin accessibility.

Purpose To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis. Methods We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ − 3 mEq/L at 48 h. Results Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n  = 48, SC n  = 42). At 48 h, mean fluid administration was 6798 ± 4850 ml vs 6574 ± 3123 ml, median anion gap 6 mEq/L (IQR 5–7) vs 7 mEq/L (IQR 5–7) and median blood ketones 0.3 mmol/L (IQR 0.1–0.5) vs 0.3 (IQR 0.1–0.5) in the PL and SC groups. DKA resolution at 48 h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73–21.16, p  = 0.111). At 24 h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68–10.72, p  = 0.002). The median ICU and hospital lengths of stay were 49 h (IQR 23–72) vs 55 h (IQR 41–80) and 81 h (IQR 58–137) vs 98 h (IQR 65–195) in the PL and SC groups. Conclusion Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.