p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation

p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the 'high-p53'Mdm4+/- mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/- background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/- mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

Stochastic models and simulation of ion channel dynamics

The behaviour of ion channels within cardiac and neuronal cells is intrinsically stochastic in nature. When the number of channels is small this stochastic noise is large and can have an impact on the dynamics of the system which is potentially an issue when modelling small neurons and drug block in cardiac cells. While exact methods correctly capture the stochastic dynamics of a system they are computationally expensive, restricting their inclusion into tissue level models and so approximations to exact methods are often used instead. The other issue in modelling ion channel dynamics is that the transition rates are voltage dependent, adding a level of complexity as the channel dynamics are coupled to the membrane potential. By assuming that such transition rates are constant over each time step, it is possible to derive a stochastic differential equation (SDE), in the same manner as for biochemical reaction networks, that describes the stochastic dynamics of ion channels. While such a model is more computationally efficient than exact methods we show that there are analytical problems with the resulting SDE as well as issues in using current numerical schemes to solve such an equation. We therefore make two contributions: develop a different model to describe the stochastic ion channel dynamics that analytically behaves in the correct manner and also discuss numerical methods that preserve the analytical properties of the model.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Some novel techniques of parameter estimation for the dynamical models in biological systems

Inverse problems based on using experimental data to estimate unknown parameters of a system often arise in biological and chaotic systems. In this paper, we consider parameter estimation in systems biology involving linear and non-linear complex dynamical models, including the Michaelis–Menten enzyme kinetic system, a dynamical model of competence induction in Bacillus subtilis bacteria and a model of feedback bypass in B. subtilis bacteria. We propose some novel techniques for inverse problems. Firstly, we establish an approximation of a non-linear differential algebraic equation that corresponds to the given biological systems. Secondly, we use the Picard contraction mapping, collage methods and numerical integration techniques to convert the parameter estimation into a minimization problem of the parameters. We propose two optimization techniques: a grid approximation method and a modified hybrid Nelder–Mead simplex search and particle swarm optimization (MH-NMSS-PSO) for non-linear parameter estimation. The two techniques are used for parameter estimation in a model of competence induction in B. subtilis bacteria with noisy data. The MH-NMSS-PSO scheme is applied to a dynamical model of competence induction in B. subtilis bacteria based on experimental data and the model for feedback bypass. Numerical results demonstrate the effectiveness of our approach.

Linear models for endocytic transformations from live cell imaging

Endocytosis is the process by which cells internalise molecules including nutrient proteins from the extracellular media. In one form, macropinocytosis, the membrane at the cell surface ruffles and folds over to give rise to an internalised vesicle. Negatively charged phospholipids within the membrane called phosphoinositides then undergo a series of transformations that are critical for the correct trafficking of the vesicle within the cell, and which are often pirated by pathogens such as Salmonella. Advanced fluorescent video microscopy imaging now allows the detailed observation and quantification of these events in live cells over time. Here we use these observations as a basis for building differential equation models of the transformations. An initial investigation of these interactions was modelled with reaction rates proportional to the sum of the concentrations of the individual constituents. A first order linear system for the concentrations results. The structure of the system enables analytical expressions to be obtained and the problem becomes one of determining the reaction rates which generate the observed data plots. We present results with reaction rates which capture the general behaviour of the reactions so that we now have a complete mathematical model of phosphoinositide transformations that fits the experimental observations. Some excellent fits are obtained with modulated exponential functions; however, these are not solutions of the linear system. The question arises as to how the model may be modified to obtain a system whose solution provides a more accurate fit.

Large scale participatory acoustic sensor data analysis : tools and reputation models to enhance effectiveness

Acoustic sensors play an important role in augmenting the traditional biodiversity monitoring activities carried out by ecologists and conservation biologists. With this ability however comes the burden of analysing large volumes of complex acoustic data. Given the complexity of acoustic sensor data, fully automated analysis for a wide range of species is still a significant challenge. This research investigates the use of citizen scientists to analyse large volumes of environmental acoustic data in order to identify bird species. Specifically, it investigates ways in which the efficiency of a user can be improved through the use of species identification tools and the use of reputation models to predict the accuracy of users with unidentified skill levels. Initial experimental results are reported.

Modelling the activation of words in human memory : the spreading activation, spooky-activation-at-a-distance and the entanglement models compared

Modelling how a word is activated in human memory is an important requirement for determining the probability of recall of a word in an extra-list cueing experiment. The spreading activation, spooky-action-at-a-distance and entanglement models have all been used to model the activation of a word. Recently a hypothesis was put forward that the mean activation levels of the respective models are as follows: Spreading � Entanglment � Spooking-action-at-a-distance This article investigates this hypothesis by means of a substantial empirical analysis of each model using the University of South Florida word association, rhyme and word norms.

Computer-intensive simulations for cellular models

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Library and information science education 2.0 : guiding principles and models of best practice. Interview with Hilary Hughes.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Bob Pymm.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Jake Wallis.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Lyn Hay.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Roy Crotty.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Mary Anne Kennan.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice. Interview with Huan Vo-Tran.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.