An alternate proof of Wise's Malnormal Special Quotient Theorem

We give an alternate proof of Wise's Malnormal Special Quotient Theorem (MSQT), avoiding cubical small cancellation theory. We also show how to deduce Wise's Quasiconvex Hierarchy Theorem from the MSQT and theorems of Hsu--Wise and Haglund--Wise.Comment: 42 pages, 10 figures. Version 2 contains minor changes, addressing referee comments. To appear in Forum of Mathematics, P

Residual finiteness, QCERF, and fillings of hyperbolic groups

We prove that if every hyperbolic group is residually finite, then every quasi-convex subgroup of every hyperbolic group is separable. The main tool is relatively hyperbolic Dehn filling.Comment: (v1) 22 pages, 2 figures. (v2) 24 pages, 2 figures. An error in the proof and statement of the main technical lemma was corrected, and some other small corrections and clarifications were mad

"Well, that was an intellectual dialogue!": how a whole-school focus on improvement shifts the substantive nature of classroom talk

This paper explores how students' talk in classrooms is influenced by a whole-school focus on lifting the quality, and the substantive nature, of classroom dialogue as an approach to improve student engagement, and to develop listening and speaking skills. Specifically, we show how designing and participating in whole-school professional learning projects emerged as a central condition for teacher and student development in the area of improving substantive classroom dialogue. The paper draws upon data from a larger, three-year empirical study in several Australian primary schools into the interconnections between professional learning, student learning, teaching and leading over time. In this paper, we focus particularly upon professional learning and its effects upon teaching and student learning, and illustrate how changing students' literacy practices require changing the practice architectures - that is, the broader conditions within which teacher and student learning occurs. Drawing on examples of teacher and student learning practices, we reveal the particular "sayings" (language), "doings" (activities), and "relatings" (relationships) which create and sustain the conditions under which students' dialogic practices can flourish. The research reveals that the practices of collaborative, critical reflexive dialogues on the part of teachers contributed significantly to the development of dialogic practices within literacy learning in classrooms

Pathogenesis of human papillomavirus-associated mucosal disease.

Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.We thank Cancer Research UK and the Medical Research Council for funding our research, some of which is described in this review.This is the accepted version of the following article: IJ Groves, N Coleman, The Journal of Pathology 2015, 235, 527–538, which has been published in final form at http://dx.doi.org/10.1002/path.449

Characterising and classifying hypothalamus development

Understanding the development of the hypothalamus is important, due to its role as the central regulator of homeostasis. However, relative to development of other regions of the brain, characterisation and understanding of hypothalamus development is incomplete. Three important reasons for this are: (i) the hypothalamus is specified early compared to other brain regions, and then develops rapidly; (ii) the hypothalamus has a complex, anatomical structure even in the embryo; (iii) hypothalamic progenitor cells grow and migrate anisotropically. This non-linear growth makes it difficult to interpret downstream developmental events and molecular interactions that regulate early hypothalamus specification and regionalisation. One promising way to investigate development of the hypothalamus is through combining computational methods and traditional embryological approaches. To this end, I begin this thesis by developing a method of fine-grained classification of the Hamburger Hamilton (HH) stage 10 chick embryo. I was able to train an accurate classifier despite a limited dataset, by testing a variety of biologically motivated data augmentation techniques. I encouraged confidence in the staging system and subsequent classifications by analysing and visualising the output of the classifier. Using this classifier, I conducted a detailed morphological study of the developing hypothalamus at HH10 and surrounding stages, using both experimental embryology techniques and computational morphometric analyses. Using my increased understanding of the developing morphology, I characterised the expression of key hypothalamus morphogens: SHH, FGF10, and BMP2, as well as components of the SHH signalling pathway. I found that regionalisation between these morphogens occurred early and rapidly, with substantial heterogeneity in expression along both the anteroposterior and mediolateral axes. Finally, I tested to what extent this regionalisation is neuroepithelium intrinsic using ex vivo culture. I found both anteroposterior and mediolateral regionalisation in culture, which suggests that these processes are self-organising in the neuroepithelium. Overall, my thesis provides novel insights into early hypothalamic morphogenesis and molecular regionalisation, and shows through extension and use of the classifier how these complex processes may begin to be unpicked

The control of human cytomegalovirus latent and lytic gene expression by chromatin remodelling

Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwin

Leading and learning: developing ecologies of educational practice

We are currently working at Charles Sturt University and in the international ‘Pedagogy, Education and Praxis’ research collaboration on a research program intended as a contribution to the development of contemporary practice theory. One focus of the program is developing an understanding of practices as living things, connected to one another in ‘ecologies of practice’. In this paper, we explore the latter concept, drawing on a current project we are conducting which explores how educational administration, professional development, and teaching and student practices may connect to one another as mutually interdependent practices, each influencing and being influenced by one another

Bromodomain Inhibitors as Therapeutics for Herpesvirus-Related Disease: All BETs Are Off?

Although the ubiquitous human herpesviruses (HHVs) are rarely associated with serious disease of the healthy host, primary infection and reactivation in immunocompromised individuals can lead to significant morbidity and, in some cases, mortality. Effective drugs are available for clinical treatment, however resistance is on the rise such that new anti-viral targets, as well as novel clinical treatment strategies, are required. A promising area of development and pre-clinical research is that of inhibitors of epigenetic modifying proteins that control both cellular functions and the viral life cycle. Here, we briefly outline the interaction of the host bromo- and extra-terminal domain (BET) proteins during different stages of the HHVs' life cycles while giving a full overview of the published work using BET bromodomain inhibitors (BRDis) during HHV infections. Furthermore, we provide evidence that small molecule inhibitors targeting the host BET proteins, and BRD4 in particular, have the potential for therapeutic intervention of HHV-associated disease

Depletion of polycistronic transcripts using short interfering RNAs: cDNA synthesis method affects levels of non-targeted genes determined by quantitative PCR.

BACKGROUND: Short interfering RNAs (siRNAs) are often used to deplete viral polycistronic transcripts, such as those encoded by human papillomavirus (HPV). There are conflicting data in the literature concerning how siRNAs targeting one HPV gene can affect levels of other genes in the polycistronic transcripts. We hypothesised that the conflict might be partly explained by the method of cDNA synthesis used prior to transcript quantification. FINDINGS: We treated HPV16-positive cervical keratinocytes with siRNAs targeting the HPV16 E7 gene and used quantitative PCR to compare transcript levels of E7 with those of E6 and E2, viral genes located upstream and downstream of the target site respectively. We compared our findings from cDNA generated using oligo-dT primers alone with those from cDNA generated using a combination of random hexamer and oligo-dT primers. Our data show that when polycistronic transcripts are targeted by siRNAs, there is a period when untranslatable cleaved mRNA upstream of the siRNA binding site remains detectable by PCR, if cDNA is generated using random hexamer primers. Such false indications of mRNA abundance are avoided using oligo-dT primers. The period corresponds to the time taken for siRNA activity and degradation of the cleaved transcripts. Genes downstream of the siRNA binding site are detectable during this interval, regardless of how the cDNA is generated. CONCLUSIONS: These data emphasise the importance of the cDNA synthesis method used when measuring transcript abundance following siRNA depletion of polycistronic transcripts. They provide a partial explanation for erroneous reports suggesting that siRNAs targeting HPV E7 can have gene-specific effects.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are