‘To the last man’—Australia’s entry to war in 1914

This paper examines the extent of an independent Australian foreign policy prior to World War I, why Britain’s declaration of war was considered to automatically include Australia, and the role of the parliament in committing Australia to war. Introduction On 31 July 1914 in an election speech at Colac in Victoria, the Opposition Leader Andrew Fisher (ALP) famously declared that ‘should the worst happen, after everything has been done that honour will permit, Australians will stand beside the mother country to help and defend her to our last man and our last shilling’. Fisher’s speech occurred in the midst of an election campaign scheduled for 5 September 1914, in what was Australia’s first double dissolution election. When Britain declared war against Germany on 4 August 1914, Sir Joseph Cook (LIB) was Prime Minister of Australia. Following the September 1914 election, Fisher took office (for the third time) and his government pursued a policy of fully supporting Britain’s war effort. This Research Paper considers the context of Fisher’s declaration by briefly outlining the steps leading to the outbreak of the war and the costs to Australia by the end of hostilities. It then examines two particular issues of relevance in the parliamentary environment: the extent of an independent Australian foreign policy and why Britain’s declaration of war was considered to automatically include Australia, and second, the role of the parliament in committing Australia to war

A Comparison of Real Time Stream Processing Frameworks

The need to process the ever-expanding volumes of information being generated daily in the modern world is driving radical changes in traditional data analysis techniques. As a result of this, a number of open source tools for handling real-time data streams has become available in recent years. Four, in particular, have gained significant traction: Apache Flink, Apache Samza, Apache Spark and Apache Storm. Despite the rising popularity of these frameworks, however, there are few studies that analyse their performance in terms of important metrics, such as throughput and latency. This study aims to correct this, by running several benchmarks against these frameworks

Octahedron-based Projections as Intermediate Representations for Computer Imaging: TOAST, TEA, and More

This paper defines and discusses a set of rectangular all-sky projections that have no singular points, notably the Tesselated Octahedral Adaptive Spherical Transformation (or TOAST) developed initially for the WorldWide Telescope. These have proven to be useful as intermediate representations for imaging data where the application transforms dynamically from a standardized internal format to a specific format (projection, scaling, orientation, etc.) requested by the user. TOAST is strongly related to the Hierarchical Triangular Mesh pixelization and is particularly well adapted to situations where one wishes to traverse a hierarchy of images increasing in resolution. Because it can be recursively computed using a very simple algorithm it is particularly adaptable to use with graphical processing units

Blindness And Poverty: An Outreach-Based, Case-Control Study Assessing The Relationship Between Poverty And Visual Impairment From Cataract In Greater Accra, Central, Eastern, Western, Volta, And Ashanti Regions Of Ghana

Background Blinding cataracts have been linked to poverty, and are the most common form of preventable blindness in the developing world. The WHO has identified cataract surgery as one of the top five potential public health interventions in developing countries; however, studies exploring the initial economic attributes before cataract surgery and subsequent outcomes following the sight-restorative surgery in the developing world have not been undertaken. This study assesses the baseline economic and sociodemographic attributes of a cohort of 267 cataract cases in rural villages throughout southern Ghana and compares them with 100 controls to test whether those with existing cataracts are more likely to be impoverished than their peers. Furthermore, this study explores the economic and sociodemographic differences of patients who elect to undergo subsidized cataract surgery compared to those who referred for cataract surgery, but do not undergo the operation. Methods and Findings An outreach-based case-control study recruited 100 control patients and 267 cataract patients at village eye care outreaches in the months of June, July, and August 2011. Cases and controls were both 20 years or older, with cases having been diagnosed with a dense/blinding cataract. Controls were excluded if they were diagnosed with a dense/blinding cataract or if their visual acuity was 20/200 or worse. Enrolled patients completed a questionnaire where the Ghana-specific Poverty Scorecard was used to indirectly assess likelihood of poverty (defined as $2.50/day purchasing power parity (PPP)). Chi-square and multivariate logistic regression showed that cases were more likely to be living below the poverty line than controls (OR 0.91 (CI 0.89, 0.94)) and were 7.29 (CI 2.89, 18.62) times as likely to be in the lowest quintile of poverty. Among cases, unadjusted OR showed that those who underwent surgery were more likely to live bellow the established poverty level than those who did not go for surgery (OR 0.96 (CI 0.93, 0.98), p=0.0392)), however, this was no longer significant when controlling for age, sex, household size, and chorionic disease status (OR 0.97 (CI 0.94, 1.00) p=0.0974). Those that went for surgery were more often male (OR 2.54 (CI 1.09, 5.95) and unemployed (OR 5.62 (CI 1.55, 20.44). Conclusions Data from this study suggests that poverty and blindness from cataracts are linked in rural villages in Ghana. Whether the downward economic trends associated with cataracts are reversed following surgery remains a valuable question that will be explored in subsequent follow-up with this cohort. Additionally, evidence suggests that future interventions and policies should target women in the uptake of the sight-restoring surgery

Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells

Breast cancer is the most common cancer and the second leading cause of cancer death in women. While ER-positive breast cancer subtypes are initially well-managed by targeted therapies targeting estrogen signaling, many women are suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients who were previously successfully treated with anti-estrogen therapies worsens overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of a tumor may allow for the possibility of customized therapy targeting each patient\u27s specific oncogene-activating mutations, and in doing so increase the probability of durable remission over the long term. Basic research on cell lines modeling different breast cancer subtypes makes possible discovery and characterization of novel driving oncogenes and their context in a breast cancer subtype model. The Wolf Hirschhorn Syndrome Candidate 1-Like 1 gene (WHSC1L1) is one of approximately 50 genes in the chromosome 8p11-p12 amplicon, an amplified region of the short arm of chromosome 8 found in 12-15% of human breast cancers, as well as other cancer types such as lung. Amplification of the 8p11-p12 region is most often found in breast cancers of the luminal B subtype. WHSC1L1 is a member of the NSD family of histone lysine methyltransferases, SET domain-containing proteins which catalyze the addition of a methyl group to lysines on the amino-terminal tail of histone H3 subunits. The WHSC1L1 gene expresses two known isoforms which code for two distinct proteins, WHSC1L1-long and WHSC1L1-short. The short isoform of WHSC1L1 codes for the first 647 of the 1437 amino acids present in the long isoform, and lacks the catalytic SET domain and several PHD and PWWP chromatin interacting domains, containing a single PWWP domain and a recently characterized acidic transactivation domain. In both normal and tumor breast tissue, WHSC1L1-short is expressed at greater levels than WHSC1L1-long. Several breast cancer cell lines established in the Ethier lab harbor WHSC1L1 amplifications and also overexpress both isoforms of WHSC1L1. The SUM44 cell line is a highly ER-positive cell line model of luminal B breast cancer isolated from a pleural effusion metastasis of a patient with aggressive disease. It is known that the short isoform of WHSC1L1, WHSC1L1-short, is a potent driving oncogene in SUM44 cells, however the specific mechanism of WHSC1L1-short as an oncomodifier is not known. To investigate WHSC1L1-short function as an oncogene in SUM44 cells, we developed an shRNA knockdown model that specifically knocked down expression of WHSC1L1-short through its unique 3\u27 UTR sequence (shWHSC1L1-short), and a model that knocked down both WHSC1L1 isoforms (shWHSC1L1-total). We found that knockdown of both total WHSC1L1 and WHSC1L1-short alone negatively affected SUM44 proliferation, and that WHSC1L1-short knockdown had a larger effect than knockdown of both isoforms. After finding that WHSC1L1 expression was required for typical proliferation rates of SUM44 cells, we performed genome-wide expression profiling of SUM44 WHSC1L1-short and total WHSC1L1 knockdown cell lines relative to a control SUM44 line transduced with shRNA against lacZ. Again we found that knockdown of the WHSC1L1-short alone had a greater affect than total WHSC1L1 knockdown, this time on the number of significantly differentially expressed genes; 1131 genes were found to be differentially expressed in the WHSC1L1-short knockdown cells relative to shLacZ control, while 238 genes were differentially expressed in the total WHSC1L1 knockdown SUM44 cells relative to shLacZ control. Interestingly, the ESR1 gene, which codes for the estrogen receptor alpha protein, was significantly downregulated by WHSC1L1-short knockdown. This was confirmed by immunoblotting with ERa antibody. While total WHSC1L1 knockdown also had a negative effect on ERa protein levels in SUM44, knockdown of WHSC1L1-short alone almost completely abrogated ERa in SUM44 as measured by western blot. We subsequently found that SUM44 cells were extremely sensitive to treatment with beta-estradiol, and that proliferation actually decreased upon as little as 100 picomolar beta-estradiol treatment, with dose-dependent decreases in proliferation as estrogen concentrations increased. We also found SUM44 cells to be relatively insensitive to Tamoxifen. Knockdown of WHSC1L1-short reduced proliferation of SUM44 cells in estrogen-free conditions, and treatment of SUM44 shWHSC1L1-short cells with increasing concentrations of beta-estradiol resulted in a marginal increase in proliferation up to 100pM beta-estradiol, then proliferation decreased with increasing beta-estradiol concentrations similar to results seen in SUM44 shLacZ control cells. After observing that WHSC1L1-short overexpression was required for expression of ERa in SUM44 cells, we asked whether knockdown of WHSC1L1-short affected genome-wide binding patterns of the estrogen receptor in SUM44 cells. Interestingly we found that ERa was binding to thousands of genomic loci in the absence of exogenous estrogen. Treatment with high doses (10nM) of beta-estradiol for 45 minutes resulted in an approximately even increase in ERa binding across sites already bound in the absence of estrogen, with some additional weak binding sites, but no significant changes in the pattern of ERa binding. No ERa binding sites were detected in SUM44 shWHSC1L1-short cells under estrogen-free conditions, and weak ERa binding was detected in SUM44 shWHSC1L1-short cells treated with 10nM beta-estradiol at loci where strong ERa binding was observed in control SUM44 cells, suggesting that WHSC1L1-short knockdown was reducing ERa expression levels, which made less ERa available to bind to chromatin in SUM44 shWHSC1L1-short cells. Our investigation of WHSC1L1 oncogenic activity in SUM44 cells resulted in the interesting observation that the short isoform of WHSC1L1 is required for expression of the estrogen receptor alpha in these cells, and that ERa is bound extensively to chromatin without activation of ERa by estrogen. SUM44 is a model for luminal B breast cancer, and is highly ER-positive, and expresses little to no progesterone receptor (PR). While the implications of ERa expression dependence on WHSC1L1-short overexpression in SUM44 cells are not yet clear, the extensive binding of ERa to estrogen response elements (ERE\u27s) in the absence of exogenous estrogen and the negative proliferative response of SUM44 to estrogen indicate that WHSC1L1 amplification and overexpression may alter the biology of the estrogen receptor in breast cancers harboring WHSC1L1 amplification and overexpression. Additionally, the differences seen in ERa binding to chromatin and the negative response of SUM44 cells to ERa agonists illustrate the importance of researching ER-positive breast cancer using additional cell line models rather than consistently using MCF7 cells to represent ER-positive disease. The dominant role of the catalytically-inactive short isoform of WHSC1L1 in regulating ERa expression and maintaining the proliferation rate of SUM44 cells suggests that catalytically inactive isoforms of chromatin modifying enzymes can be important regulators of gene expression. Interestingly, recent work has shown that WHSC1L1-short is likely not regulating target gene expression through histone methylation, but instead is acting as a co-factor for a different chromatin-binding complex, the BRD4-CHD8 complex, which has been shown to be recruited to superenhancer regions (marked by histone acetylation) by WHSC1L1-short, which results in activation of pTEFb through BRD4 and directly activates target gene transcription. It will be important to avoid assumptions about binding substrate identities of catalytically inactive isoforms of future chromatin modifiers of interest, as the catalytically inactive isoforms of these genes may also bind to chromatin substrates unrelated to the substrate of the catalytically active isoform

Online Modeling and Tuning of Parallel Stream Processing Systems

Writing performant computer programs is hard. Code for high performance applications is profiled, tweaked, and re-factored for months specifically for the hardware for which it is to run. Consumer application code doesn\u27t get the benefit of endless massaging that benefits high performance code, even though heterogeneous processor environments are beginning to resemble those in more performance oriented arenas. This thesis offers a path to performant, parallel code (through stream processing) which is tuned online and automatically adapts to the environment it is given. This approach has the potential to reduce the tuning costs associated with high performance code and brings the benefit of performance tuning to consumer applications where otherwise it would be cost prohibitive. This thesis introduces a stream processing library and multiple techniques to enable its online modeling and tuning. Stream processing (also termed data-flow programming) is a compute paradigm that views an application as a set of logical kernels connected via communications links or streams. Stream processing is increasingly used by computational-x and x-informatics fields (e.g., biology, astrophysics) where the focus is on safe and fast parallelization of specific big-data applications. A major advantage of stream processing is that it enables parallelization without necessitating manual end-user management of non-deterministic behavior often characteristic of more traditional parallel processing methods. Many big-data and high performance applications involve high throughput processing, necessitating usage of many parallel compute kernels on several compute cores. Optimizing the orchestration of kernels has been the focus of much theoretical and empirical modeling work. Purely theoretical parallel programming models can fail when the assumptions implicit within the model are mis-matched with reality (i.e., the model is incorrectly applied). Often it is unclear if the assumptions are actually being met, even when verified under controlled conditions. Full empirical optimization solves this problem by extensively searching the range of likely configurations under native operating conditions. This, however, is expensive in both time and energy. For large, massively parallel systems, even deciding which modeling paradigm to use is often prohibitively expensive and unfortunately transient (with workload and hardware). In an ideal world, a parallel run-time will re-optimize an application continuously to match its environment, with little additional overhead. This work presents methods aimed at doing just that through low overhead instrumentation, modeling, and optimization. Online optimization provides a good trade-off between static optimization and online heuristics. To enable online optimization, modeling decisions must be fast and relatively accurate. Online modeling and optimization of a stream processing system first requires the existence of a stream processing framework that is amenable to the intended type of dynamic manipulation. To fill this void, we developed the RaftLib C++ template library, which enables usage of the stream processing paradigm for C++ applications (it is the run-time which is the basis of almost all the work within this dissertation). An application topology is specified by the user, however almost everything else is optimizable by the run-time. RaftLib takes advantage of the knowledge gained during the design of several prior streaming languages (notably Auto-Pipe). The resultant framework enables online migration of tasks, auto-parallelization, online buffer-reallocation, and other useful dynamic behaviors that were not available in many previous stream processing systems. Several benchmark applications have been designed to assess the performance gains through our approaches and compare performance to other leading stream processing frameworks. Information is essential to any modeling task, to that end a low-overhead instrumentation framework has been developed which is both dynamic and adaptive. Discovering a fast and relatively optimal configuration for a stream processing application often necessitates solving for buffer sizes within a finite capacity queueing network. We show that a generalized gain/loss network flow model can bootstrap the process under certain conditions. Any modeling effort, requires that a model be selected; often a highly manual task, involving many expensive operations. This dissertation demonstrates that machine learning methods (such as a support vector machine) can successfully select models at run-time for a streaming application. The full set of approaches are incorporated into the open source RaftLib framework

WorldWide Telescope in Research and Education

The WorldWide Telescope computer program, released to researchers and the public as a free resource in 2008 by Microsoft Research, has changed the way the ever-growing Universe of online astronomical data is viewed and understood. The WWT program can be thought of as a scriptable, interactive, richly visual browser of the multi-wavelength Sky as we see it from Earth, and of the Universe as we would travel within it. In its web API format, WWT is being used as a service to display professional research data. In its desktop format, WWT works in concert (thanks to SAMP and other IVOA standards) with more traditional research applications such as ds9, Aladin and TOPCAT. The WWT Ambassadors Program (founded in 2009) recruits and trains astrophysically-literate volunteers (including retirees) who use WWT as a teaching tool in online, classroom, and informal educational settings. Early quantitative studies of WWTA indicate that student experiences with WWT enhance science learning dramatically. Thanks to the wealth of data it can access, and the growing number of services to which it connects, WWT is now a key linking technology in the Seamless Astronomy environment we seek to offer researchers, teachers, and students alike.Comment: 4 pages, 2 figures, describes software available at worldwidetelescope.or

Modeling the Formation of Clouds in Brown Dwarf Atmospheres

Because the opacity of clouds in substellar mass object (SMO) atmospheres depends on the composition and distribution of particle sizes within the cloud, a credible cloud model is essential for accurately modeling SMO spectra and colors. We present a one--dimensional model of cloud particle formation and subsequent growth based on a consideration of basic cloud microphysics. We apply this microphysical cloud model to a set of synthetic brown dwarf atmospheres spanning a broad range of surface gravities and effective temperatures (g_surf = 1.78 * 10^3 -- 3 * 10^5 cm/s^2 and T_eff = 600 -- 1600 K) to obtain plausible particle sizes for several abundant species (Fe, Mg2SiO4, and Ca2Al2SiO7). At the base of the clouds, where the particles are largest, the particle sizes thus computed range from ~5 microns to over 300 microns in radius over the full range of atmospheric conditions considered. We show that average particle sizes decrease significantly with increasing brown dwarf surface gravity. We also find that brown dwarfs with higher effective temperatures have characteristically larger cloud particles than those with lower effective temperatures. We therefore conclude that it is unrealistic when modeling SMO spectra to apply a single particle size distribution to the entire class of objects.Comment: 25 pages; 8 figures. We have added considerable detail describing the physics of the cloud model. We have also added discussions of the issues of rainout and the self-consistent coupling of clouds with brown dwarf atmospheric models. We have updated figures 1, 3, and 4 with new vertical axis labels and new particle sizes for forsterite and gehlenite. Accepted to the Astrophysical Journal, Dec. 2, 200