776 research outputs found
Origins and phenotypic heterogeneity of macrophages in endometriosis
No full textEndometriosis is a chronic inflammatory disorder associated with pelvic pain and infertility that affects ~176 million reproductive age women worldwide. It is defined by the presence of endometrial-like tissue outside the uterus (lesions). The aetiology of endometriosis is not fully understood however we know that menstrual effluent is refluxed into the peritoneal cavity during menstruation in 90% of women, and it is hypothesised that in some women this tissue can adhere to form lesions (Sampsons theory). Current management of endometriosis is unsatisfactory and there is an unmet need for new treatments. Macrophages play a key role in the growth, vascularisation and innervation of endometriosis lesions. We know from other diseases such as cancer that macrophages with differential origins and phenotypes play distinct roles in disease development, however our current knowledge of macrophage origins, recruitment pathways and phenotype in endometriosis is limited. In this thesis I aimed to define the origin of lesion-resident macrophages, the recruitment pathways active in disease and assess lesion macrophage phenotypic heterogeneity using the Edinburgh mouse model of endometriosis. This mouse model mimics the retrograde reflux of menses material by stimulating an artificial menstruation-like event in mice, whereby this tissue is collected and injected into the peritoneal cavity of recipient mice. I hypothesised that lesion resident macrophages have multiple origins, that CCL2 is an important chemokine for macrophage recruitment and that multiple macrophage populations exist within endometriosis lesions that have differential phenotypic profiles.
I used Csf1r-EGFP mice (MacGreen; macrophages express green fluorescent protein) to characterise the origins of lesion resident macrophages. Endometriosis was induced in WT mice using donor endometrial tissue from Csf1r-EGFP mice. 16% of lesion macrophages were GFP+ endometrial-derived macrophages and the remaining 84% were GFP- infiltrating macrophages of recipient origin. To assess infiltration of tissue-resident large peritoneal macrophages (LPM) and monocytederived small peritoneal macrophages (SPM) into lesions, I adoptively transferred LPM or SPM (isolated from Csf1r-EGFP mice) into the peritoneal cavity of endometriosis mice. GFP+ LPM infiltrated lesions however GFP+ SPM were not identified within lesion tissue. Using Ly6C, F4/80 dual immunofluorescence I identified both Ly6C+ monocytes and Ly6C+ F4/80+ monocyte-derived macrophages in lesions.
Mice with endometriosis exhibited a ~3 fold increase of peritoneal macrophages expressing CCR2 (receptor for chemokine (C-C) motif ligand 2 (CCL2)) compared to sham controls and 53% of lesion resident macrophages expressed CCR2. To assess the importance of CCR2 in the development of endometriosis lesions, endometriosis was induced in CCR2 knockout mice compared to WT. CCR2 knockout mice developed a similar number of endometriosis lesions to WT mice and exhibited an influx of Ly6C+ monocytes into the peritoneal cavity, which also infiltrated into lesions. Notably, endometriosis lesions from CCR2 knockout animals had fewer F4/80+ macrophages. CCL2 knockout mice developed more endometriosis lesions than WT and demonstrated similar infiltration of Ly6C+ monocytes and F4/80+ macrophages into lesion tissue compared to WT. Importantly, CCL2 knockout mice had an increase in CD45+ leukocytes within the peritoneal cavity which could have attributed to the difference observed in lesion number.
Initially, I performed flow cytometry analysis on lesion tissue to assess phenotypic heterogeneity and demonstrated that multiple macrophage populations were present, based on differential expression of CCR2, MHC II, CX3CR1 and CD86. I also observed that endometrial macrophage phenotypic heterogeneity was lost upon incorporation into lesions, suggesting macrophage reprogramming upon incorporation into the lesion microenvironment. To gain further granularity into the phenotypic heterogeneity of lesion macrophages, using single-cell RNA-sequencing, I performed unbiased transcriptional profiling of CD45+ cells in lesions (6006 cells), donor endometrial tissue (1306 cells) and peritoneal lavage cells from sham (5645 cells) and endometriosis mice (6720 cells). Clustering analysis identified 5 lesionresident macrophage populations that had differential transcriptomic profiles. Comparison of lesion-resident macrophage populations with macrophage clusters from endometrial tissue and the peritoneum confirmed that lesions contained macrophages from different origins.
Collectively, these results indicate that lesion resident macrophages are derived from multiple origins and that 5 different macrophage populations exist within lesions that have differential transcriptomic profiles. Macrophage/monocyte recruitment may be in part mediated by the CCL2/CCR2 signalling pathway but when this pathway is disrupted in our model of endometriosis there appears to be compensation such that monocytes are still recruited to the peritoneal cavity and lesions. Herein, I provide an important insight into macrophage biology in endometriosis and provide a platform for further studies that aim to identify disease-specific macrophage populations that could potentially be targeted for clinical benefit
Urban settlement in Emilia Romagna: Between spontaneous development, grid-planning and post-antique adaptation
No full textIl contributo prende in esame l'insediamento antico in Emilia Romagna e il suo impatto postantico proponendo un'analisi che muove dall'assetto e dalla distribuzione dei centri urbani antichi per individuarne, da una prospettiva originale, le persistenze di lungo periodo, i condizionamenti imposti alle città postantiche dal medioevo ad oggi, l'impatto sull'organizzazione territoriale odierna
Spacetime symmetries and the CPT theorem
No full textThis dissertation explores several issues related to the CPT theorem.
Chapter 2 explores the meaning of spacetime symmetries in general and time reversal in particular. It is proposed that a third conception of time reversal, 'geometric time reversal', is more appropriate for certain theoretical purposes than the existing 'active' and 'passive' conceptions. It is argued that, in the case of classical electromagnetism, a particular nonstandard time reversal operation is at least as defensible as the standard view. This unorthodox time reversal operation is of interest because it is the classical counterpart of a view according to which the so-called 'CPT theorem' of quantum field theory is better called 'PT theorem'; on this view, a puzzle about how an operation as apparently non-spatio-temporal as charge conjugation can be linked to spacetime symmetries in as intimate a way as a CPT theorem would seem to suggest dissolves.
In chapter 3, we turn to the question of whether the CPT theorem is an essentially quantum-theoretic result. We state and prove a classical analogue of the CPT theorem for systems of tensor fields. This classical analogue, however, appears not to extend to systems of spinor fields. The intriguing answer to our question thus appears to be that the CPT theorem for spinors is essentially quantum-theoretic, but that the CPT theorem for tensor fields applies equally to the classical and quantum cases.
Chapter4 explores a puzzle that arises when one puts the CPT theorem alongside a standard way of understanding spacetime symmetries, according to which (latter) spacetime symmetries are to be understood in terms of background spacetime structure. The puzzle is that a 'PT theorem' amounts to a statement that the theory may not make essential use of a preferred direction of time, and this seems odd. We propose a solution to that puzzle for the case of tensor field theories.Ph.D.Includes bibliographical references (p. 102)
Australian Author Marion Halligan - Word Artist
No full textAustralian author Marion Halligan admits that her life has been 'centred in domesticity' and this is where she draws on much of the material for her fiction. This could also be a reason why her work has been critically overlooked. Halligan is adept at capturing details of life in the domestic realm and weaving poignant, thought-provoking stories about experiences all of us can recognise in our own lives. It does not take the discerning reader long to discover the deeper considerations in her writing. According to Halligan, 'the world is a cruel and dark and difficult place and it is words that light the small candle flames that keep the dark at bay'[1]. Words and writing are essential to Halligan's life. In an essay titled 'Why I Write', she says: 'I write in order to put the world into words. I've always done that in my head. I can't perceive anything without trying to find words for it'[2]. Halligan's writing is an evocative exploration of the human condition. For Halligan, 'it is artists showing you what they see that educates the heart, in novels, in paintings, in photographs'.[3] The following essay examines three of Halligan's novels which feature an artist protagonist who is struggling to come to terms with the experience of loss, grief and bereavement. Lovers' Knots (1992), The Golden Dress (1998) and The Fog Garden (2001) are rich evocations of lives which are 'a walk with love and death ... The same subjects as the Greeks, and Shakespeare. [The] characters aren't kings and queens, aren't noble and grand, but their passions are as real'[4]
Picture Browsing and Map Interaction using a Projector Phone.
No full textIt is expected that projector phones (mobile phones with built-in pico projectors) will hit the market by 2010. Such phones provide a completely new way to display information and interaction techniques. The system presented in this paper allows the simulation of these projector phones as the real devices are not yet available. Through this, we demonstrate that it is currently possible to design, develop and evaluate applications for projector phones. The system supports three different modalities in order to compare when which display (phone display, projection) should be used. This prototype system was used for the implementation of two applications in order to test the advantages and disadvantages of projector phones for two common scenarios, picture browsing and map interaction. This demonstration paper describes the hardware used for the simulation of projector phones and the two developed prototypes. These prototypes were used for two different studies discussed in [1] and [2]
Review Of Dublin\u27s Merchant-Quaker: Anthony Sharp And The Community Of Friends, 1643-1707 By R. L. Greaves
No full textGreaves, author of several well-documented books on 17th-century dissenters, argues that Anthony Sharp (1643-1707) represents the transformation of Irish Friends from a charismatic sect into a respectable Protestant denomination. Sharp, whose father gave him several hundred pounds to begin business, ended by owning a woolen manufactory with 500 workers, at least 29 houses, and several thousand acres of land. Converted c. 1663, he became a minister, clerk and treasurer of various meetings, a controversialist who defended Friends against religious and political opponents, and a strict enforcer of the discipline. The meeting used Sharp\u27s legal training and business skills in a wide variety of activities: arbitrating between members, defending those persecuted for tithes, planning buildings, documenting persecutions, and raising money for schools. He emerges as devoted to the welfare of the Quaker community, but with no sympathy for Irish Catholics. Like George Whitehead, the leader of English Quakers after Fox\u27s death, Sharp showed little intellectual originality in his writings or activities for the meeting. Greaves\u27s account provides valuable new information about this significant sect whose Irish members numbered less than 5,000. For collections specializing in history of religion and Ireland. Upper-division undergraduates and above
Dynamic simulation of a light-weight, low-drag, hybrid-electric sports coupe
No full textThe University of Queensland UltraCommuter concept is an ultra-light, low-drag, hybrid-electric sports coupe designed to minimize energy consumption and environmental impact while enhancing the performance, styling, features and convenience that motorists enjoy. This paper presents a detailed simulation study of the vehicle's performance and fuel economy using ADVISOR, including a detailed description of the component models and parameters assumed. Results from the study include predictions of a 0-100kph acceleration time o
Caribbean Report 05-04-1999
No full text1. Headlines with anchor Keith Stone Greaves (00:25)2. British media report that the US commitment to the refugee crisis and war in the Balkans in Kosovo could involve the movement of 20, 000 Albanians to the US navy base in Guantanamo Bay in Cuba and the Pacific island of Guam. Professor Bert Thomas, Director of Caribbean Studies at City University in New York comments on the movement of war refugees to Cuba. Kimberly Andrews Thomas reports (00:26 - 03:26)3. Trinidad and Tobago Attorney General Ramesh Lawrence Maharaj discusses the legal rulings by the Privy Council preventing the country from implementing the death penalty. Keith Stone Greaves reports (03:27 – 06:46)4. In Antigua/Barbuda tourism is viewed as the main economic sector and main foreign exchange income earner, providing jobs for 75 percent of the population. The Antiguan government estimates the sector growth at 7 percent annum. Antigua hotel and tourism consultant Nova Alexander speaks on the absence of Antiguans in top level management positions in the tourist industry. Keith Stone Greaves reports (06:47 – 11:23)5. Trinidad and Tobago is at the forefront in calls for a Caribbean Court of Justice which will replace the Privy Council in London and act as a final court of appeal for Caribbean judicial matters. Attorney General Ramesh Lawrence Maharaj discusses the regional position and CARICOM commitment to establishing the court of appeal. Keith Stone Greaves reports (11:24 – 14: 58
Queen's road near Grahamstown
No full textBuilt from 1837-1842 by Andrew Geddes Bain, this highway connected Grahamstown with the military posts and forts established after the 6th Frontier War
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