Towards Bayesian experimental design for nonlinear models that require a large number of sampling times

The use of Bayesian methodologies for solving optimal experimental design problems has increased. Many of these methods have been found to be computationally intensive for design problems that require a large number of design points. A simulation-based approach that can be used to solve optimal design problems in which one is interested in finding a large number of (near) optimal design points for a small number of design variables is presented. The approach involves the use of lower dimensional parameterisations that consist of a few design variables, which generate multiple design points. Using this approach, one simply has to search over a few design variables, rather than searching over a large number of optimal design points, thus providing substantial computational savings. The methodologies are demonstrated on four applications, including the selection of sampling times for pharmacokinetic and heat transfer studies, and involve nonlinear models. Several Bayesian design criteria are also compared and contrasted, as well as several different lower dimensional parameterisation schemes for generating the many design points.

Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions

The resection of DNA double-strand breaks (DSBs) to generate ssDNA tails is a pivotal event in the cellular response to these breaks. In the two-step model of resection, primarily elucidated in yeast, initial resection by Mre11-CtIP is followed by extensive resection by two distinct pathways involving Exo1 or BLM/WRN-Dna2. However, resection pathways and their exact contributions in humans in vivo are not as clearly worked out as in yeast. Here, we examined the contribution of Exo1 to DNA end resection in humans in vivo in response to ionizing radiation (IR) and its relationship with other resection pathways (Mre11-CtIP or BLM/WRN). We find that Exo1 plays a predominant role in resection in human cells along with an alternate pathway dependent on WRN. While Mre11 and CtIP stimulate resection in human cells, they are not absolutely required for this process and Exo1 can function in resection even in the absence of Mre11-CtIP. Interestingly, the recruitment of Exo1 to DNA breaks appears to be inhibited by the NHEJ protein Ku80, and the higher level of resection that occurs upon siRNA-mediated depletion of Ku80 is dependent on Exo1. In addition, Exo1 may be regulated by 53BP1 and Brca1, and the restoration of resection in BRCA1-deficient cells upon depletion of 53BP1 is dependent on Exo1. Finally, we find that Exo1-mediated resection facilitates a transition from ATM- to ATR-mediated cell cycle checkpoint signaling. Our results identify Exo1 as a key mediator of DNA end resection and DSB repair and damage signaling decisions in human cells.

Double blind : women as creative practice-led researchers

While the productive relationship between praxis and feminist research has been well established, the situation is more complicated for female artist/researchers in the fraught field of creative practice-led research. Firstly, their research is being conducted in the context of ongoing debate, as Andrea Phillips has summarized, over whether practice-led research has been embraced in order to potentially produce emancipatory knowledge, or whether it is simply the rationalization and quantification of creative processes. Secondly, there is a pervasive paradox whereby, rather than feeling empowered by the process of critical and reflective self-analysis, many women are inhibited by enduring insecurities about the value of their work and/or their ownership of it. The reasons for this appear to be twofold: they are disheartened by the ongoing disproportion of successful women artists, and they are intimidated by the fundamentally masculine discourse surrounding research in the university. Many of these anxieties appear to have been exacerbated by the research quality assessment process, the Excellence in Research for Australia Initiative (ERA). This collaborative paper draws on the authors' experiences as both artist-researchers and educators to contextualize this paradox and also discuss what forms of praxis intervention may be useful in the preparation for, and supervision of, creative practice-led research by women.

Glider path-planning for optimal sampling of mesocale eddies

Ocean gliders constitute an important advance in the highly demanding ocean monitoring scenario. Their effciency, endurance and increasing robustness make these vehicles an ideal observing platform for many long term oceanographic applications. However, they have proved to be also useful in the opportunis-tic short term characterization of dynamic structures. Among these, mesoscale eddies are of particular interest due to the relevance they have in many oceano-graphic processes.

Layered double hydroxides as iodine sorbents

This study investigates the potential of a Zn/Al layered double hydroxides (LHDs) as an adsorbent for the removal of iodine species from potable water (Theiss et al., 2011b). In this paper the resultant materials were characterised using powder x-ray diffraction (XRD) and thermogravimetry (TG) coupled with evolved gas mass spectrometry (EGMS) (Frost, et al, 2005, Rives, et al, 2001).

Collective sampling and analysis of high order tensors for chatroom communications

This work investigates the accuracy and efficiency tradeoffs between centralized and collective (distributed) algorithms for (i) sampling, and (ii) n-way data analysis techniques in multidimensional stream data, such as Internet chatroom communications. Its contributions are threefold. First, we use the Kolmogorov-Smirnov goodness-of-fit test to show that statistical differences between real data obtained by collective sampling in time dimension from multiple servers and that of obtained from a single server are insignificant. Second, we show using the real data that collective data analysis of 3-way data arrays (users x keywords x time) known as high order tensors is more efficient than centralized algorithms with respect to both space and computational cost. Furthermore, we show that this gain is obtained without loss of accuracy. Third, we examine the sensitivity of collective constructions and analysis of high order data tensors to the choice of server selection and sampling window size. We construct 4-way tensors (users x keywords x time x servers) and analyze them to show the impact of server and window size selections on the results.

Cause of Death, Trend and Disease Burden in Shandong Province, China : the Third Retrospective Sampling Survey of Cause of Death Report

This book describes the mortality for all causes of death and the trend in major causes of death since 1970s in Shandong Province, China.

Sex discrimination and non-random sampling in the Australian labour market

Historically a significant gap between male and female wages has existed in the Australian labour market. Indeed this wage differential was institutionalised in the 1912 arbitration decision which determined that the basic female wage would be set at between 54 and 66 per cent of the male wage. More recently however, the 1969 and 1972 Equal Pay Cases determined that male/female wage relativities should be based upon the premise of equal pay for work of equal value. It is important to note that the mere observation that average wages differ between males and females is not sine qua non evidence of sex discrimination. Economists restrict the definition of wage discrimination to cases where two distinct groups receive different average remuneration for reasons unrelated to differences in productivity characteristics. This paper extends previous studies of wage discrimination in Australia (Chapman and Mulvey, 1986; Haig, 1982) by correcting the estimated male/female wage differential for the existence of non-random sampling. Previous Australian estimates of male/female human capital basedwage specifications together with estimates of the corresponding wage differential all suffer from a failure to address this issue. If the sample of females observed to be working does not represent a random sample then the estimates of the male/female wage differential will be both biased and inconsistent.

Thermogravimetric analysis of selected layered double hydroxides

Thermogravimetric analysis (TG) and powder X-ray diffraction (PXRD) were used to study some selected Mg/Al and Zn/Al layered double hydroxides (LDHs) prepared by co-precipitation. A Mg/Al hydrotalcite was investigated before and after reformation in fluoride and nitrate solutions. Little change in the TG or PXRD patterns was observed. It was proposed that successful intercalation of nitrate anions has occurred. However, the absence of any change in the d(003) interlayer spacing suggests that fluoride anions were not intercalated between the LDH layers. Any fluoride anions that were removed from solution are most likely adsorbed onto the outer surfaces of the hydrotalcite. As fluoride removal was not quantified it is not possible to confirm that this has happened without further experimentation. Carbonate is probably intercalated into the interlayer of these hydrotalcites, as well as fluoride or nitrate. The carbonate most likely originates from either incomplete decarbonation during thermal activation or adsorption from the atmosphere or dissolved in the deionised water. Small and large scale co-precipitation syntheses of a Zn/Al LDH were also investigated to determine if there was any change in the product. While the small scale experiment produced a good quality LDH of reasonable purity; the large scale synthesis resulted in several additional phases. Imprecise measurement and difficulty in handling the large quantities of reagents appeared to be sufficient to alter the reaction conditions causing a mixture of phases to be formed.

Removal of boron species by layered double hydroxides : a review

Boron, which is an essential element for plants, is toxic to humans and animals at high concentrations. Layered double hydroxides (LDHs) and thermally activated LDHs have shown good uptake of a range of boron species in laboratory scale experiments when compared to current available methods, which are for the most part ineffective or prohibitively expensive. LDHs were able to remove anions from water by anion exchange, the reformation (or memory) effect and direct precipitation. The main mechanism of boron uptake appeared to be anion exchange, which was confirmed by powder X-ray diffraction (XRD) measurements. Solution pH appeared to have little effect on boron sorption while thermal activation did not always significantly improve boron uptake. In addition, perpetration of numerous LDHs with varying boron anions in the interlayer region by direct co-precipitation and anion exchange have been reported by a number of groups. The composition and orientation of the interlayer boron ions could be identified with reasonable certainty by applying a number of characterisation techniques including: powder XRD, nuclear magnetic resonance spectroscopy (NMR), X-ray photoelectron spectroscopy (XPS) and infrared (IR) spectroscopy. There is still considerable scope for future research on the application of LDHs for the removal of boron contaminants.

Chromatin modifications involved in the DNA damage response to double strand breaks

In eukaryotes, genomic DNA is tightly compacted into a protein-DNA complex known as chromatin. This dense structure presents a barrier to DNA-dependent processes including transcription, replication and DNA repair. The repressive structure of chromatin is overcome by ATP-dependent chromatin remodelling complexes and chromatin-modifying enzymes. There is now ample evidence that DNA double-strand breaks (DSBs) elicit various histone modifications (such as acetylation, deacetylation, and phosphorylation) that function combinatorially to control the dynamic structure of the chromatin microenvironment. The role of these mechanisms during transcription and replication has been well studied, while the research into their impact on regulation of DNA damage response is rapidly gaining momentum. How chromatin structure is remodeled in response to DNA damage and how such alterations influence DSB repair are currently significant questions. This review will summarise the major chromatin modifications and chromatin remodelling complexes implicated in the DNA damage response to DSBs.

Half metallicity in a zigzag double-walled nanotube nanodot : an Ab initio prediction

Ab initio density functional calculations were performed to study finite-length zigzag (7, 0) @ (16, 0) double-walled carbon nanotubes (DWCNTs) with H-termination at the open ends. We find that such a DWCNT nanodot displays a very large magnetic moment at the zigzag edges and the ground state displays symmetric anti-ferromagnetic coupling. When an external electric field is applied along the direction of tube axis, a gap is opened for one spin channel, whereas another spin channel remains metallic, i.e. half metallicity occurs. Our results suggest an important new avenue for the development of CNT-based spintronic materials with enhanced properties.

Community response to disasters in Indonesia : Gotong Royong; a double edged-sword

Indonesia is a country spread across wide-ranging archipelago, located in South East Asia between two oceans, the Indian and the Pacific. Indonesia is well known as an active tectonic region because it lies on top of three major active tectonic plates: the Eurasian in the North, the Indian Ocean-Australian in the South, and the Pacific plate in the East. The southern and eastern part of the country features a range of volcanic arcs, volcanic mountains, and lowlands with 500 young volcanoes, of which 128 are active and thus representing 15% of the world’s active volcanoes. In the period 2002-2007, approximately 1782 disasters occurred, with hundreds of thousands of lives lost and billions of rupiah in losses incurred: (Floods - 1183 instances, cyclones - 272 instances, and landslides - 252 instances). Of these, the 2004 Aceh tsunami and the 2006 central Java earthquake (impacting predominantly city and suburbs of Yogyakarta) were the most significant. Even so, disaster management experts believe lessons learnt from the two major natural disasters needs to be formalised into laws and institutions before another disaster occurs, regardless of the type of natural disaster – i.e. Volcano eruption or landslide; as opposed to tsunami or earthquake. Following in the wake of disasters occurring in Yogyakarta, many of its community members responded by banding together as one, with the determination of rebuilding its villages and cities through the spirit of ‘gotong royong’. The idea of social interaction; in particular as a collective, consensual, and cooperative nation; has predominantly formed the ideological basis of Indonesia’s societal nature. Many Indonesian terms cohere to this ideology, such as: ‘koperasi” (cooperatives as the basis of economic interactions), ‘musyawarah’ (consensual nature in decision making), and ‘gotong royong’ (mutual assistance). ‘Gotong royong’ has become a key cultural operator in Indonesia, in particular In Jogjakarta. Appropriately so as ‘gotong royong’ is depicted from the traditional Javanese village, where labour is accomplished through reciprocal exchange and the villagers are motivated by a general ethos of selfishness and concern for the common good. The culture of ‘gotong royong’ promotes positive values such as social harmony and mutual reciprocation in disaster-affected areas provides the necessary spirit needed to endure the hardships and for all involved. While gotong royong emphasises the positive notions of mutual family support and deep community level activity there is a potential for contrast against government lead disaster response and recovery management activities especially in settings where sporadic governance mechanisms exist and transparency and accountability in the recovery process of public infrastructure assets have been questioned. This paper thus questions whether Gotong Royong is a double-edged sword, and explores the potential marriage of community values and governance mechanisms for future disaster management planning and practice.

Double tax agreements and the international allocation of business income in Australia

Increasingly, the effectiveness of the present system of taxation of international businesses is being questioned. The problem associated with the taxation of such businesses is twofold. A system of international taxation must be a fair and equitable system, distributing profits between the relevant jurisdictions and, in doing so, avoiding double taxation. At the same time, the prevention of fiscal evasion must be secured. In an attempt to achieve a fair and equitable system Australia adopts unilateral, bilateral and multilateral measures to avoid double taxation and restrict the avoidance of tax. The first step in ascertaining the international allocation of business income is to consider the taxation of business income according to domestic law, that is, the unilateral measures. The treatment of international business income under the Australian domestic law, that is, the Income Tax Assessment Act 1936 (Cth) and Income Tax Assessment Act 1997 (Cth), will depend on two concepts, first, whether the taxpayer is a resident of Australia and secondly, whether the income is sourced in Australia. After the taxation of business profits has been determined according to domestic law it is necessary to consider the applicability of the bilateral measures, that is, the Double Tax Agreements (DTAs) to which Australia is a party, as the DTAs will override the domestic law where there is any conflict. Australia is a party to 40 DTAs with another seven presently being negotiated. The preamble to Australia's DTAs provides that the purpose of such agreements is 'to conclude an Agreement for the avoidance of double taxation and the prevention of fiscal evasion with respect to taxes on income'. Both purposes, for different reasons, are equally important. It has been said that: The taxpayer hopes the treaty will prevent the double taxation of his income; the tax gatherer hopes the treaty will prevent fiscal evasion; and the politician just hopes. The first purpose, the avoidance of double taxation, is achieved through the provision of rules whereby the Contracting States agree to the classification of income and the allocation of that income to a particular State. In this sense DTAs do not allocate jurisdiction to tax but rather provide an arrangement whereby the States agree to restrict their substantive law. The restriction is either through the non-taxing of the income or via the provision of a tax credit.