Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

The impact of nonlinear exposure risk relationships on seasonal time series data: modelling danish neonatal birth anthropometric data

Background Birth weight and length have seasonal fluctuations. Previous analyses of birth weight by latitude effects identified seemingly contradictory results, showing both 6 and 12 monthly periodicities in weight. The aims of this paper are twofold: (a) to explore seasonal patterns in a large, Danish Medical Birth Register, and (b) to explore models based on seasonal exposures and a non-linear exposure-risk relationship. Methods Birth weight and birth lengths on over 1.5 million Danish singleton, live births were examined for seasonality. We modelled seasonal patterns based on linear, U- and J-shaped exposure-risk relationships. We then added an extra layer of complexity by modelling weighted population-based exposure patterns. Results The Danish data showed clear seasonal fluctuations for both birth weight and birth length. A bimodal model best fits the data, however the amplitude of the 6 and 12 month peaks changed over time. In the modelling exercises, U- and J-shaped exposure-risk relationships generate time series with both 6 and 12 month periodicities. Changing the weightings of the population exposure risks result in unexpected properties. A J-shaped exposure-risk relationship with a diminishing population exposure over time fitted the observed seasonal pattern in the Danish birth weight data. Conclusion In keeping with many other studies, Danish birth anthropometric data show complex and shifting seasonal patterns. We speculate that annual periodicities with non-linear exposure-risk models may underlie these findings. Understanding the nature of seasonal fluctuations can help generate candidate exposures.

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

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 educative practice in helping to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice : interview with John Terrell

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 Kate Davis.

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.

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.

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.