title: Spatio-temporal modelling of crime using low discrepancy sequences

authors: Brown, Paul T.

abstract: We perform spatio-temporal modelling of burglary data in order to predict areas of high criminal risk for local authorities. We wish to account for several spatio-temporal factors as latent processes to make the model as realistic as possible, thus creating a model with a large latent eld with several hyperparameters. Analysis of the model is done using Integrated Nested Laplace Approximations (INLA) (Rue et al. 2009), a fast Bayesian inference methodology that provides more computationally efficient estimations than Markov Chain Monte Carlo (MCMC) methods.

text: Spatio-temporal modelling of crime using low discrepancy sequences We perform spatio-temporal modelling of burglary data in order to predict areas of high criminal risk for local authorities. We wish to account for several spatio-temporal factors as latent processes to make the model as realistic as possible, thus creating a model with a large latent eld with several hyperparameters. Analysis of the model is done using Integrated Nested Laplace Approximations (INLA) (Rue et al. 2009), a fast Bayesian inference methodology that provides more computationally efficient estimations than Markov Chain Monte Carlo (MCMC) methods.

year: 2016

title: Identifying the signalling pathway of a novel  Myostatin Splice Variant (MSV)

authors: Hennebry, Alex

subjects: myostatin

abstract: Myostatin (Mstn), a member of the transforming growth factor-β super family, is a potent negative regulator of skeletal muscle mass. Studies delineating the function of Mstn have identified multiple signal transduction pathways that convey the Mstn signal. Mstn has been shown to influence canonical TGF-β, mitogen activated protein kinase (MAPK) and the PI3K/AKT signal transduction cascades. The discovery in our laboratory of a novel splice variant of Mstn (MSV) that opposes Mstn and stimulates the proliferation of myoblasts provided the impetus for the investigations in this thesis. The splicing of MSV was restricted to the Cetartiodactyl clade of mammals, and MSV may represent an intragenic regulator of Mstn. Thus, the studies undertaken in this thesis were to delineate the signalling pathways used by Mstn and MSV in order to understand how their opposing roles in myoblasts regulate myogenesis.
Initially, microarray analysis was used to investigate the transcriptional responses of ovine myoblasts following exposure to recombinant Mstn (eukaryotic) and MSV (prokaryotic) protein. Mstn treatment induced changes in number of transcripts, with changes consistent with previous investigations, for example increased interlukin-6 (IL6) and decreased MyoD. In addition, a novel transcriptional target of Mstn, the β1 subunit of the Na⁺-K⁺-ATPase was discovered. Treatment of ovine myoblasts with recombinant MSV induced a plethora of transcriptional responses. IPA analysis suggested a number of these were due to LPS (endotoxin) contamination, which could be attributed to the production of this protein in E. coli. This was confirmed using the Limulus amebocyte lysate assay. Phase separation using Triton-X 114 proved an effective method for the removal of LPS from the MSV preparation.
Western blot analysis was performed following the treatment of ovine myoblasts with Mstn and purified MSV. Consistent with previous myoblast studies Mstn stimulated canonical TGF-β (Smad) signalling and the p38 and ERK components of the MAPK signalling cascade. In contrast to previous studies, Mstn also stimulated AKT signalling, with specific phosphorylation of serine 473 (AKTS⁴⁷³). In addition, Mstn altered the abundance of multiple myogenic transcription factors (MyoD, Myf5, MRF4, Pax7 and Mef2) and the abundance and/or the phosphorylation of targets that have a metabolic role in skeletal muscle (rps6, 4EBP1 and p70S6K). Treatment with MSV increased the abundance of Smad 3, Myf5, 4EBP1 and stimulated AKTS⁴⁷³and 4EBP1 phosphorylation. These data provided the foundation for confirmation of these pathways targeted by MSV in C₂C₁₂ myoblasts that stably expressed MSV.
C₂C₁₂ cells expressing MSV had an increased proliferative capacity and showed increased mitochondrial activity (EZ4U assay) as compared to controls. These cells showed an increased abundance of the MRFs MyoD, MRF4 and Myogenin and an increased abundance or phosphorylation of signalling targets involved in canonical TGF-β, MAPK and PI3K/AKT signalling cascades. In addition, cells expressing MSV had an increased abundance and phosphorylation of acetyl co-enzyme A carboxylase (ACC) and 4EBP1, which have established roles in regulating metabolism and the synthesis of protein.
The significant overlap of processes influenced by the Na⁺ , K⁺ ATPase complex and Mstn prompted an investigation on how Mstn regulates the β1 subunit of the Na⁺ , K⁺ ATPase. This transcriptional response was found to be dependent on the Smad pathway. In addition, these studies also show that Na⁺ K⁺ ATPase activity plays a role in proliferation and differentiation of ovine myoblasts and suggest that Mstn inhibits ion flow controlled through the function of this enzyme complex. 
In conclusion, these studies show that Mstn and MSV share a number of common signalling targets. In contrast to previous studies of Mstn, the stable expression MSV increases the activation of AKT signalling and increases the abundance of key myogenic transcription factors. In addition, MSV increases the abundance and phosphorylation of ACC and 4EBP1, molecules involved regulating the synthesis of protein and fatty acids. In addition, the β1 subunit of the Na⁺ K⁺ ATPase, was identified as a novel transcriptional target of Mstn, with this regulation controlled through a Smad dependant mechanism. These data confirm the postulate that Mstn and MSV have divergent signalling functions and suggest a role for MSV in the control of oxidative metabolism.

text: Identifying the signalling pathway of a novel  Myostatin Splice Variant (MSV) Myostatin (Mstn), a member of the transforming growth factor-β super family, is a potent negative regulator of skeletal muscle mass. Studies delineating the function of Mstn have identified multiple signal transduction pathways that convey the Mstn signal. Mstn has been shown to influence canonical TGF-β, mitogen activated protein kinase (MAPK) and the PI3K/AKT signal transduction cascades. The discovery in our laboratory of a novel splice variant of Mstn (MSV) that opposes Mstn and stimulates the proliferation of myoblasts provided the impetus for the investigations in this thesis. The splicing of MSV was restricted to the Cetartiodactyl clade of mammals, and MSV may represent an intragenic regulator of Mstn. Thus, the studies undertaken in this thesis were to delineate the signalling pathways used by Mstn and MSV in order to understand how their opposing roles in myoblasts regulate myogenesis.
Initially, microarray analysis was used to investigate the transcriptional responses of ovine myoblasts following exposure to recombinant Mstn (eukaryotic) and MSV (prokaryotic) protein. Mstn treatment induced changes in number of transcripts, with changes consistent with previous investigations, for example increased interlukin-6 (IL6) and decreased MyoD. In addition, a novel transcriptional target of Mstn, the β1 subunit of the Na⁺-K⁺-ATPase was discovered. Treatment of ovine myoblasts with recombinant MSV induced a plethora of transcriptional responses. IPA analysis suggested a number of these were due to LPS (endotoxin) contamination, which could be attributed to the production of this protein in E. coli. This was confirmed using the Limulus amebocyte lysate assay. Phase separation using Triton-X 114 proved an effective method for the removal of LPS from the MSV preparation.
Western blot analysis was performed following the treatment of ovine myoblasts with Mstn and purified MSV. Consistent with previous myoblast studies Mstn stimulated canonical TGF-β (Smad) signalling and the p38 and ERK components of the MAPK signalling cascade. In contrast to previous studies, Mstn also stimulated AKT signalling, with specific phosphorylation of serine 473 (AKTS⁴⁷³). In addition, Mstn altered the abundance of multiple myogenic transcription factors (MyoD, Myf5, MRF4, Pax7 and Mef2) and the abundance and/or the phosphorylation of targets that have a metabolic role in skeletal muscle (rps6, 4EBP1 and p70S6K). Treatment with MSV increased the abundance of Smad 3, Myf5, 4EBP1 and stimulated AKTS⁴⁷³and 4EBP1 phosphorylation. These data provided the foundation for confirmation of these pathways targeted by MSV in C₂C₁₂ myoblasts that stably expressed MSV.
C₂C₁₂ cells expressing MSV had an increased proliferative capacity and showed increased mitochondrial activity (EZ4U assay) as compared to controls. These cells showed an increased abundance of the MRFs MyoD, MRF4 and Myogenin and an increased abundance or phosphorylation of signalling targets involved in canonical TGF-β, MAPK and PI3K/AKT signalling cascades. In addition, cells expressing MSV had an increased abundance and phosphorylation of acetyl co-enzyme A carboxylase (ACC) and 4EBP1, which have established roles in regulating metabolism and the synthesis of protein.
The significant overlap of processes influenced by the Na⁺ , K⁺ ATPase complex and Mstn prompted an investigation on how Mstn regulates the β1 subunit of the Na⁺ , K⁺ ATPase. This transcriptional response was found to be dependent on the Smad pathway. In addition, these studies also show that Na⁺ K⁺ ATPase activity plays a role in proliferation and differentiation of ovine myoblasts and suggest that Mstn inhibits ion flow controlled through the function of this enzyme complex. 
In conclusion, these studies show that Mstn and MSV share a number of common signalling targets. In contrast to previous studies of Mstn, the stable expression MSV increases the activation of AKT signalling and increases the abundance of key myogenic transcription factors. In addition, MSV increases the abundance and phosphorylation of ACC and 4EBP1, molecules involved regulating the synthesis of protein and fatty acids. In addition, the β1 subunit of the Na⁺ K⁺ ATPase, was identified as a novel transcriptional target of Mstn, with this regulation controlled through a Smad dependant mechanism. These data confirm the postulate that Mstn and MSV have divergent signalling functions and suggest a role for MSV in the control of oxidative metabolism.

year: 2014

title: Ngā whakaaro o ngā ākonga: perspectives and experiences of Māori students in outdoor education in Aotearoa New Zealand

authors: Washbourn, Phil

subjects: Outdoor education

abstract: This study aims to develop an understanding of the perspectives and experiences of Māori students in a secondary school outdoor education programme in Aotearoa New Zealand. Lynch (2012) indicated that “there is a clear need, and wide scope, for research into: cultural elements of outdoor education programmes; cultural effects on participants; culturally appropriate research approaches and programme effects on, and experiences of, people who identify as Māori” (p.49). Outdoor education in Aotearoa New Zealand has been heavily influenced by ‘Eurocentric’ values and practices that contrast with those of Te Ao Māori. In line with a number of calls to re-envision the field, the perspectives and experiences of Māori and the incorporation of Te Ao Māori pedagogies are vital to the reconstruction of an integrated and inclusive Aotearoa New Zealand expression of Outdoor Education for the 21st century.
This study, guided by culturally responsive research methodology, used focus groups to investigate the opinions, thoughts and expectations of Māori students of outdoor education. Thematic analysis was used to analyse the focus group data, and four major themes were identified: the importance of shared experience and relationships to positive experiences of outdoor education; the distinctive practices of outdoor education make learning enjoyable and engaging; the importance to students of making connections with Te Ao Māori through experience, stories of places and history; and the complexity of engaging Māori in participation in outdoor education, including factors such as affordability, the influence of friends and whānau and prioritising educational pathways. A range of practices and approaches from Te Ao Māori are considered and presented, based on the contribution of the student participants, including pedagogical principles from Te Ao Māori such as wānanga, whanaungatanga and tauira. Suggestions for practice include developing connections within the community and experiencing Te Ao Māori learning contexts such as waka ama, noho marae and mahinga kai.

text: Ngā whakaaro o ngā ākonga: perspectives and experiences of Māori students in outdoor education in Aotearoa New Zealand This study aims to develop an understanding of the perspectives and experiences of Māori students in a secondary school outdoor education programme in Aotearoa New Zealand. Lynch (2012) indicated that “there is a clear need, and wide scope, for research into: cultural elements of outdoor education programmes; cultural effects on participants; culturally appropriate research approaches and programme effects on, and experiences of, people who identify as Māori” (p.49). Outdoor education in Aotearoa New Zealand has been heavily influenced by ‘Eurocentric’ values and practices that contrast with those of Te Ao Māori. In line with a number of calls to re-envision the field, the perspectives and experiences of Māori and the incorporation of Te Ao Māori pedagogies are vital to the reconstruction of an integrated and inclusive Aotearoa New Zealand expression of Outdoor Education for the 21st century.
This study, guided by culturally responsive research methodology, used focus groups to investigate the opinions, thoughts and expectations of Māori students of outdoor education. Thematic analysis was used to analyse the focus group data, and four major themes were identified: the importance of shared experience and relationships to positive experiences of outdoor education; the distinctive practices of outdoor education make learning enjoyable and engaging; the importance to students of making connections with Te Ao Māori through experience, stories of places and history; and the complexity of engaging Māori in participation in outdoor education, including factors such as affordability, the influence of friends and whānau and prioritising educational pathways. A range of practices and approaches from Te Ao Māori are considered and presented, based on the contribution of the student participants, including pedagogical principles from Te Ao Māori such as wānanga, whanaungatanga and tauira. Suggestions for practice include developing connections within the community and experiencing Te Ao Māori learning contexts such as waka ama, noho marae and mahinga kai.

year: 2018