Oestrogen-modulated gene expression in the human endometrium

To identify key regulatory mechanisms in the growth and development of the human endometrium, microarray analysis was performed on uncultured human endometrium collected during menstruation (M) and the late-proliferative (LATE-P)-phase of the menstrual cycle, as well as after 24 h incubation in the presence of oestradiol (17beta-E2). We demonstrate the expression of novel gene transcripts in the human endometrium. i.e. mucin-9, novel oestrogen-responsive gene transcripts, i.e. gelsolin and flotillin-1, and genes known to be expressed in human endometrium but not yet shown to be oestrogen responsive, i.e. connexin-37 and TFF1/pS2. Genes reported to be expressed during the implantation window and implicated in progesterone action, i.e. secretoglobin family 2A, member 2 (mammaglobin) and homeobox-containing proteins, were up-regulated in uncultured LATE-P-phase endometrium compared to M-phase endometrium. Some gene transcripts are regulated directly by 17beta-E2 alone, others are influenced by the in vivo environment as well. These observations emphasise that the regulation of endometrium maturation by oestrogen entails more then just stimulation of cell proliferation.

Performance profiling for predictive train schedules

In this article an alternate sensitivity analysis is proposed for train schedules. It characterises the schedules robustness or lack thereof and provides unique profiles of performance for different sources of delay and for different values of delay. An approach like this is necessary because train schedules are only a prediction of what will actually happen. They can perform poorly with respect to a variety of performance metrics, when deviations and other delays occur, if for instance they can even be implemented, and as originally intended. The information provided by this analytical approach is beneficial because it can be used as part of a proactive scheduling approach to alter a schedule in advance or to identify suitable courses of action for specific “bad behaviour”. Furthermore this information may be used to quantify the cost of delay. The effect of sectional running time (SRT) deviations and additional dwell time in particular were quantified for three railway schedule performance measures. The key features of this approach were demonstrated in a case study.

Fred’s Flow (Canada) and Murphy Well (Australia) : thick komatiitic lava flows with contrasting compositions, emplacement mechanisms and water contents

Two Archaean komatiitic flows, Fred’s Flow in Canada and the Murphy Well Flow in Australia, have similar thicknesses (120 and 160 m) but very different compositions and internal structures. Their contrasting differentiation profiles are keys to determine the cooling and crystallization mechanisms that operated during the eruption of Archaean ultramafic lavas. Fred’s Flow is the type example of a thick komatiitic basalt flow. It is strongly differentiated and consists of a succession of layers with contrasting textures and compositions. The layering is readily explained by the accumulation of olivine and pyroxene in a lower cumulate layer and by evolution of the liquid composition during downward growth of spinifex-textured rocks within the upper crust. The magmas that erupted to form Fred’s Flow had variable compositions, ranging from 12 to 20 wt% MgO, and phenocryst contents from 0 to 20 vol%. The flow was emplaced by two pulses. A first ~20-m-thick pulse was followed by another more voluminous but less magnesian pulse that inflated the flow to its present 120 m thickness. Following the second pulse, the flow crystallized in a closed system and differentiated into cumulates containing 30–38 wt% MgO and a residual gabbroic layer with only 6 wt% MgO. The Murphy Well Flow, in contrast, has a remarkably uniform composition throughout. It comprises a 20-m-thick upper layer of fine-grained dendritic olivine and 2–5 vol% amygdales, a 110–120 m intermediate layer of olivine porphyry and a 20–30 m basal layer of olivine orthocumulate. Throughout the flow, MgO contents vary little, from only 30 to 33 wt%, except for the slightly more magnesian basal layer (38–40 wt%). The uniform composition of the flow and dendritic olivine habits in the upper 20 m point to rapid cooling of a highly magnesian liquid with a composition like that of the bulk of the flow. Under equilibrium conditions, this liquid should have crystallized olivine with the composition Fo94.9, but the most magnesian composition measured by electron microprobe in samples from the flow is Fo92.9. To explain these features, we propose that the parental liquid contained around 32 wt% MgO and 3 wt% H2O. This liquid degassed during the eruption, creating a supercooled liquid that solidified quickly and crystallized olivine with non-equilibrium textures and compositions.

Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks

Purpose The majority of cancer patients will receive radiotherapy (RT), therefore, investigations into advances of this modality are important. Conventional RT dose intensities are limited by adverse responses in normal tissues and a primary goal is to ameliorate adverse normal tissue effects. The aim of these experiments is to further our understanding regarding the mechanism of radioprotection by the DNA minor groove binder, methylproamine, in a cellular context at the DNA level. Materials and methods We used immunocytochemical methods to measure the accumulation of phosphorylated H2AX (γH2AX) foci following ionizing radiation (IR) in patient-derived lymphoblastoid cells exposed to methylproamine. Furthermore, we performed pulsed field gel electrophoresis DNA damage and repair assays to directly interrogate the action of methylproamine on DNA in irradiated cells. Results We found that methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence of methylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay. Conclusions These results suggest that methylproamine acts by preventing the formation of DNA double-strand breaks (dsbs) and support the hypothesis that radioprotection by methylproamine is mediated, at least in part, by decreasing initial DNA damage.

Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.

Identifying influential users of micro-blogging services : a dynamic action-based network approach

In this paper, we present a dynamic model to identify influential users of micro-blogging services. Micro-blogging services, such as Twitter, allow their users (twitterers) to publish tweets and choose to follow other users to receive tweets. Previous work on user influence on Twitter, concerns more on following link structure and the contents user published, seldom emphasizes the importance of interactions among users. We argue that, by emphasizing on user actions in micro-blogging platform, user influence could be measured more accurately. Since micro-blogging is a powerful social media and communication platform, identifying influential users according to user interactions has more practical meanings, e.g., advertisers may concern how many actions – buying, in this scenario – the influential users could initiate rather than how many advertisements they spread. By introducing the idea of PageRank algorithm, innovatively, we propose our model using action-based network which could capture the ability of influential users when they interacting with micro-blogging platform. Taking the evolving prosperity of micro-blogging into consideration, we extend our actionbaseduser influence model into a dynamic one, which could distinguish influential users in different time periods. Simulation results demonstrate that our models could support and give reasonable explanations for the scenarios that we considered.

Reduced motor facilitation during action observation in schizophrenia : a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

Nonprofit Service Delivery for Government : Accountability Relationships and Mechanisms

When government purchases social services under contract from a nonprofit organisation, a clear accountability relationship is created. The NPO must give an account for the use of the funds and achievement of outcomes to the funder. This paper explores how accountability is enacted in two different types of funding relationships in Queensland. Support is found for the argument that different relationships have different approaches to accountability.

Sortase A : an ideal target for anti-virulence drug development

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.

Learning about and taking action for the environment : child and teacher experiences in a preschool water education program

Water education and conservation programs have grown exponentially in Australian primary and secondary schools and, although early childhood services have been slower to respond to the challenges of sustainability, they are catching up fast. One early program targeted at preschools was the Water Aware Centre Program in northern New South Wales developed by the local water supply authority. This paper reports on a qualitative study of children’s and teachers’ experiences of the program in three preschools. The study’s aim was to identify program attributes and pedagogies that supported learning and action taking for water conservation, and to investigate if and how the program influenced children’s and teachers’practices. Data were collected through an interview with the program designer, conversations with child participants of the program, and a qualitative survey with early childhood staff. A three-step thematic analysis was conducted on the children’s and teachers’ data. Findings revealed that the program expanded children and teachers’ ideas about water conservation and increased their water conservation practices. The children were found to influence the water conservation practices of the adults around them, thus changing practices at school and at home.

A clarion call for action based on refined DALY estimates for South Africa

Initial estimates of the burden of disease in South Africa in 20001 have been revised on the basis of additional data to estimate the disability-adjusted life-years (DALYs) for single causes for the first time in South Africa. The findings highlight the fact that despite uncertainty in the estimates, they provide important information to guide public health responses to improve the health of the nation...

A theory of process modeling impact

Process modeling – the design and use of graphical documentations of an organization’s business processes – is a key method to document and use information about the operations of businesses. Still, despite current interest in process modeling, this research area faces essential challenges. Key unanswered questions concern the impact of process modeling in organizational practice, and the mechanisms through which impacts are developed. To answer these questions and to provide a better understanding of process modeling impact, I turn to the concept of affordances. Affordances describe the possibilities for goal-oriented action that a technical object offers to a user. This notion has received growing attention from IS researchers. The purpose of my research is to further develop the IS discipline’s understanding of affordances and impacts from information objects, such as process models used by analysts for information systems analysis and design. Specifically, I seek to extend existing theory on the emergence, perception and actualization of affordances. I develop a research model that describes the process by which affordances emerge between an individual and an object, how affordances are perceived, and how they are actualized by the individual. The proposed model also explains the role of available information for the individual, and the influence of perceived actualization effort. I operationalize and test this research model empirically, using a full-cycle, mixed methods study consisting of case study and experiment.