Colorectal Cancer Through Simulation and Experiment

Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the ‘Hallmarks of Cancer’ has been extended in recent times and provides an excellent basis for future research. We present a timely summary of the literature relating to colorectal cancer, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. We conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that mathematical and computational modelling can provide

Quantum Hall induced currents and the magnetoresistance of a quantum point contact

We report an investigation of quantum Hall induced currents by simultaneous measurements of their magnetic moment and their effect on the conductance of a quantum point contact (QPC). Features in the magnetic moment and QPC resistance are correlated at Landau-level filling factors nu=1, 2 and 4, which demonstrates the common origin of the effects. Temperature and non-linear sweep rate dependences are observed to be similar for the two effects. Furthermore, features in the noise of the induced currents, caused by breakdown of the quantum Hall effect, are observed to have clear correlations between the two measurements. In contrast, there is a distinct difference in the way that the induced currents decay with time when the sweeping field halts at integer filling factor. We attribute this difference to the fact that, while both effects are sensitive to the magnitude of the induced current, the QPC resistance is also sensitive to the proximity of the current to the QPC split-gate. Although it is clearly demonstrated that induced currents affect the electrostatics of a QPC, the reverse effect, the QPC influencing the induced current, was not observed

CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

PRH/HHEX (Proline Rich Homeodomain protein/Haematopoietically-Expressed Homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA binding activity, increased cleavage of PRH by the proteasome, and the misregulation of PRH target genes. Here we show that PRH and hyperphosphorylated PRH are present in normal prostate epithelial cells, and that hyperphosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion

Immune response to rabies vaccination in pediatric transplant patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75049/1/j.1399-3046.2008.00936.x.pd

Area and individual differences in personal crime victimization incidence: The role of individual, lifestyle/routine activities and contextual predictors

This article examines how personal crime differences between areas and between individuals are predicted by area and population heterogeneity and their synergies. It draws on lifestyle/routine activities and social disorganization theories to model the number of personal victimization incidents over individuals including routine activities and area characteristics, respectively, as well as their (cross-cluster) interactions. The methodology employs multilevel or hierarchical negative binomial regression with extra binomial variation using data from the British Crime Survey and the UK Census. Personal crime rates differ substantially across areas, reflecting to a large degree the clustering of individuals with measured vulnerability factors in the same areas. Most factors suggested by theory and previous research are conducive to frequent personal victimization except the following new results. Pensioners living alone in densely populated areas face disproportionally high numbers of personal crimes. Frequent club and pub visits are associated with more personal crimes only for males and adults living with young children, respectively. Ethnic minority individuals experience fewer personal crimes than whites. The findings suggest integrating social disorganization and lifestyle theories and prioritizing resources to the most vulnerable, rather than all, residents of poor and densely populated areas to prevent personal crimes

Earliest Triassic microbialites in the South China Block and other areas; controls on their growth and distribution

Earliest Triassic microbialites (ETMs) and inorganic carbonate crystal fans formed after the end-Permian mass extinction (ca. 251.4 Ma) within the basal Triassic Hindeodus parvus conodont zone. ETMs are distinguished from rarer, and more regional, subsequent Triassic microbialites. Large differences in ETMs between northern and southern areas of the South China block suggest geographic provinces, and ETMs are most abundant throughout the equatorial Tethys Ocean with further geographic variation. ETMs occur in shallow-marine shelves in a superanoxic stratified ocean and form the only widespread Phanerozoic microbialites with structures similar to those of the Cambro-Ordovician, and briefly after the latest Ordovician, Late Silurian and Late Devonian extinctions. ETMs disappeared long before the mid-Triassic biotic recovery, but it is not clear why, if they are interpreted as disaster taxa. In general, ETM occurrence suggests that microbially mediated calcification occurred where upwelled carbonate-rich anoxic waters mixed with warm aerated surface waters, forming regional dysoxia, so that extreme carbonate supersaturation and dysoxic conditions were both required for their growth. Long-term oceanic and atmospheric changes may have contributed to a trigger for ETM formation. In equatorial western Pangea, the earliest microbialites are late Early Triassic, but it is possible that ETMs could exist in western Pangea, if well-preserved earliest Triassic facies are discovered in future work

Applied Theatre and Practice as Research: Polyphonic Conversations

Applied theatre practice as research might be perceived as a curious conflation. Not greatly foregrounded in the literature on applied theatre or performance practice as research, this article engages with the particularities of such a pairing. Beginning with identifying why a consideration is timely, ‘the practice as research’ and ‘social’ turns are invoked and analysed as relevant contexts to consider applied theatre practice as research. Two projects are offered, providing specific examples for discussion. Revealed by increased scrutiny, some broader epistemological questions emerge concerning power, hierarchy of knowledge and research ‘authoring’. A metaphor of polyphonic conversations is offered as an amplification of the applied theatre practical research methodological terrain. Encouraging the basis of many sets of voices contributing to research and potentially negotiating concerns about power hierarchies and knowledge production, the metaphor provokes a fluidity of epistemology, including expanding on the now familiar debates around theory and practice particularly relevant for socially engaged performance-related practical research