The Australian Labor Party (ALP) split over conscription has usually been interpreted as arising from the actions of William Morris (Billy) Hughes on the one side, in conflict with various forces ...within the labour movement on the other. However, this bipolar view ignores the role of the Governor-General Sir Ronald Munro Ferguson who had been proactive in Australian domestic politics from 1914 in order to maximise the war effort on Britain's behalf and to enhance his own office. His firm belief that conscription was necessary and Hughes was the only man capable of being Prime Minister led him to work behind the scenes to secure those objectives. He was also suspicious of the ALP and its ties with the Catholic community that he saw as linked to Irish disloyalty and so supported counter-intelligence measures against them. This article examines how this largely overlooked vice-regal involvement contributed to the political upheaval in this period.
Coordination of fate transition and cell division is crucial to maintain the plant architecture and to achieve efficient production of plant organs. In this paper, we analysed the stem cell dynamics ...at the shoot apical meristem (SAM) that is one of the plant stem cells locations. We designed a mathematical model to elucidate the impact of hormonal signaling on the fate transition rates between different zones corresponding to slowly dividing stem cells and fast dividing transit amplifying cells. The model is based on a simplified two-dimensional disc geometry of the SAM and accounts for a continuous displacement towards the periphery of cells produced in the central zone. Coupling growth and hormonal signaling results in a nonlinear system of reaction-diffusion equations on a growing domain with the growth rate depending on the model components. The model is tested by simulating perturbations in the level of key transcription factors that maintain SAM homeostasis. The model provides new insights on how the transcription factor HECATE is integrated in the regulatory network that governs stem cell differentiation.
•We present a preconditioned conjugate gradient method for geostatistical inversion.•The prior covariance matrix is used as preconditioner at negative computational cost.•The approach incorporates ...linearized uncertainty quantification.•The method is particularly efficient for the inversion of transient data.•Transient inversion may speed up experiments and improve quality of inversion results.
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In the geostatistical inverse problem of subsurface hydrology, continuous hydraulic parameter fields, in most cases hydraulic conductivity, are estimated from measurements of dependent variables, such as hydraulic heads, under the assumption that the parameter fields are autocorrelated random space functions. Upon discretization, the continuous fields become large parameter vectors with O(104−107) elements. While cokriging-like inversion methods have been shown to be efficient for highly resolved parameter fields when the number of measurements is small, they require the calculation of the sensitivity of each measurement with respect to all parameters, which may become prohibitive with large sets of measured data such as those arising from transient groundwater flow.
We present a Preconditioned Conjugate Gradient method for the geostatistical inverse problem, in which a single adjoint equation needs to be solved to obtain the gradient of the objective function. Using the autocovariance matrix of the parameters as preconditioning matrix, expensive multiplications with its inverse can be avoided, and the number of iterations is significantly reduced. We use a randomized spectral decomposition of the posterior covariance matrix of the parameters to perform a linearized uncertainty quantification of the parameter estimate.
The feasibility of the method is tested by virtual examples of head observations in steady-state and transient groundwater flow. These synthetic tests demonstrate that transient data can reduce both parameter uncertainty and time spent conducting experiments, while the presented methods are able to handle the resulting large number of measurements.
Consent, capacity and the right to say no Bastian, Peter D; Eng, Adeleen; Denson, Linley A ...
Medical journal of Australia,
05/2015, Letnik:
202, Številka:
8
Journal Article
Attempts by retail workers to limit their hours of employment through campaigns for the early closing of shops have received only limited attention. Yet, Sydney's drapery community played a ...longstanding and prominent role in this movement. In the 1880s, Thomas Caddy helped foster an alliance, now completely forgotten, between the Drapers' Association and the Sydney Trades and Labor Council to campaign for early closing by moral suasion. These moves ended in failure and revealed the problems associated with using moral suasion tactics, the fluidity of early worker affiliations, the strengths and limitations of early peak union councils and the changing status of workers within the drapery trade.
We report the characterisation of 27 cardiovascular-related traits in 23 inbred mouse strains. Mice were phenotyped either in response to chronic administration of a single dose of the ...beta-adrenergic receptor blocker atenolol or under a low and a high dose of the beta-agonist isoproterenol and compared to baseline condition. The robustness of our data is supported by high trait heritabilities (typically H(2)>0.7) and significant correlations of trait values measured in baseline condition with independent multistrain datasets of the Mouse Phenome Database. We then focused on the drug-, dose-, and strain-specific responses to beta-stimulation and beta-blockade of a selection of traits including heart rate, systolic blood pressure, cardiac weight indices, ECG parameters and body weight. Because of the wealth of data accumulated, we applied integrative analyses such as comprehensive bi-clustering to investigate the structure of the response across the different phenotypes, strains and experimental conditions. Information extracted from these analyses is discussed in terms of novelty and biological implications. For example, we observe that traits related to ventricular weight in most strains respond only to the high dose of isoproterenol, while heart rate and atrial weight are already affected by the low dose. Finally, we observe little concordance between strain similarity based on the phenotypes and genotypic relatedness computed from genomic SNP profiles. This indicates that cardiovascular phenotypes are unlikely to segregate according to global phylogeny, but rather be governed by smaller, local differences in the genetic architecture of the various strains.
β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative ...contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β(1)-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.
Neuron morphology is frequently used to classify cell-types in the mammalian cortex. Apart from the shape of the soma and the axonal projections, morphological classification is largely defined by ...the dendrites of a neuron and their subcellular compartments, referred to as dendritic spines. The dimensions of a neuron’s dendritic compartment, including its spines, is also a major determinant of the passive and active electrical excitability of dendrites. Furthermore, the dimensions of dendritic branches and spines change during postnatal development and, possibly, following some types of neuronal activity patterns, changes depending on the activity of a neuron. Due to their small size, accurate quantitation of spine number and structure is difficult to achieve (Larkman, J Comp Neurol 306:332,
1991
). Here we follow an analysis approach using high-resolution EM techniques.
Serial block-face scanning electron microscopy
(SBFSEM) enables automated imaging of large specimen volumes at high resolution. The large data sets generated by this technique make manual reconstruction of neuronal structure laborious. Here we present NeuroStruct, a reconstruction environment developed for fast and automated analysis of large SBFSEM data sets containing individual stained neurons using optimized algorithms for CPU and GPU hardware. NeuroStruct is based on 3D operators and integrates image information from image stacks of individual neurons filled with biocytin and stained with osmium tetroxide. The focus of the presented work is the reconstruction of dendritic branches with detailed representation of spines. NeuroStruct delivers both a 3D surface model of the reconstructed structures and a 1D geometrical model corresponding to the skeleton of the reconstructed structures. Both representations are a prerequisite for analysis of morphological characteristics and simulation signalling within a neuron that capture the influence of spines.
Doublecortin (DCX) domains serve as protein-interaction platforms. Mutations in members of this protein superfamily are linked to several genetic diseases. Mutations in the human DCX gene result in ...abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, and DCDC2 has been associated with dyslectic reading disabilities.
The DCX-repeat gene family is composed of eleven paralogs in human and in mouse. Its evolution was followed across vertebrates, invertebrates, and was traced to unicellular organisms, thus enabling following evolutionary additions and losses of genes or domains. The N-terminal and C-terminal DCX domains have undergone sub-specialization and divergence. Developmental in situ hybridization data for nine genes was generated. In addition, a novel co-expression analysis for most human and mouse DCX superfamily-genes was performed using high-throughput expression data extracted from Unigene. We performed an in-depth study of a complete gene superfamily using several complimentary methods.
This study reveals the existence and conservation of multiple members of the DCX superfamily in different species. Sequence analysis combined with expression analysis is likely to be a useful tool to predict correlations between human disease and mouse models. The sub-specialization of some members due to restricted expression patterns and sequence divergence may explain the successful addition of genes to this family throughout evolution.
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