Virtual software in reality

Software visualisation is an important weapon in the program comprehension armoury. It is a technique that can, when designed and used effectively, aid in understanding existing program code. It can achieve this by displaying information in new and different forms, which may make obvious something missed in reading the code. It can also be used to present many aspects of the data at once. Software, despite many software engineering advances in requirements, design and implementation techniques, continues to be complex and large and if anything seems to be growing in these respects. This means that techniques that failed to aid comprehension and maintenance are certainly not going to be able to deal with the current software. Therefore this area requires research to be able to suggest solutions to deal with the information overload that is sure to occur. There are several issues that this thesis addresses; all of them related to the creation of software visualisation systems that are capable of being used and useful well into the next generation of software systems. The scale and complexity of software are pressing issues, as is the associated information overload problem that this brings. In an attempt to address this problem the following are considered to be important: abstractions, representations, mappings, metaphors, and visualisations. These areas are interrelated and the first four enable the final one, visualisations. These problems are not the only ones that face software visualisation systems. There are many that are based on the general theory of the applicability of the technique to such tasks as program comprehension, rather than the detail of how a particular code fragment is shown. These problems are also related to the enabling technology of three- dimensional visualisations; virtual reality. In summary the areas of interest are: automation, evolution, scalability, navigation and interaction, correlation, and visual complexity. This thesis provides an exploration of these identified areas in the context of software visualisation. Relationships that describe, and distinguish between, existing and future software visualisations are presented, with examples based on recent software visualisation research. Two real world metaphors (and their associated mappings and representations) are defined for the purpose of visualising software as an aid to program comprehension. These metaphors also provide a vehicle for the exploration of the areas identified above. Finally, an evaluation of the visualisations is presented using a framework developed for the comparative evaluation of three-dimensional, comprehension oriented, software visualisations. This thesis has shown the viability of using three-dimensional software visualisations. The important issues of automation, evolution, scalability, and navigation have been presented and discussed, and their relationship to real world metaphors examined. This has been done in conjunction with an investigation into the use of such real world metaphors for software visualisation. The thesis as a whole has provided an important examination of many of the issues related to these types of visualisation in the context of software and is therefore a valuable basis for future work in this area

"We Really Help, Taking Care of Each Other": Older Homeless Adults as Caregivers.

Objectives:Many older homeless adults maintain contact with family. We conducted a qualitative study examining the role of family caregiving for older homeless adults. Method:We conducted semi-structured qualitative interviews with a sample of 46 homeless participants who reported spending at least one night with a housed family member in the prior 6 months. Results:A total of 13 of 46 older adult participants provided caregiving. Themes included (a) the death of the care recipient led to the participant's homelessness; (b) feeling a duty to act as caregivers; (c) providing care in exchange for housing; (d) caregivers' ability to stay was tenuous; (e) providing care conflicted with the caregiver's needs; and (f) resentment when family was ungrateful. Discussion:In a sample of older homeless adults in contact with family, many provided caregiving for housed family. For some, caregiving precipitated homelessness; for others, caregiving provided temporary respite from homelessness, and for others, caregiving continued during homelessness

Enemy Films on Soviet Screens:Trophy Films during the Early Cold War, 1947-52

The Soviet Union fought a cultural war on two fronts during the final years of Stalin’s leadership. The first front faced inward, against the legacy of the Great Patriotic War and how it was won: against the effects of wartime liberalization and fraternization with the West. The second front faced outward, against the infiltration of Western culture in the context of the emerging Cold Wa

Sustained Microglial Immune Responses in an SIV/Macaque Model of HIV CNS Disease

Human Immunodeficiency Virus (HIV) central nervous system (CNS) disease remains a significant clinical issue in the post-antiretroviral therapy (ART) era. Although the severity of HIV CNS disease has decreased with ART, the prevalence has not changed. It is hypothesized that chronic inflammation in the CNS despite effective viral suppression is critical to the pathogenesis of HIV CNS disease. As one of the immune cells in the brain that is also chronically infected with HIV, microglia are of particular interest. In this dissertation, we characterized chronic microglial immune activation in an SIV/pigtailed macaque model of HIV CNS disease. We characterized in this model the expression colony stimulating factor 1 receptor (CSF1R), a classic tyrosine kinase receptor that is constitutively expressed on cells of the myeloid lineage that is essential for the survival of microglia. Additionally, overexpression of CSF1R has been associated with several neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In animals with SIV encephalitis, we found that CSF1R was significantly elevated in brain compared to uninfected animals. Interestingly, CSF1R protein levels remained elevated in the brains of ART-suppressed SIV-infected animals, suggesting that CSF1R plays a role in the persistence of HIV CNS disease in the post-ART era. We also characterized a similar receptor, triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 is similarly associated with AD and ALS, and there is significant crosstalk between TREM2 and CSF1R via DNAX adaptor protein 12 (DAP12). Consequently, TREM2 and CSF1R have many of the same downstream signaling effects in microglia. While TREM2 and CSF1R both significantly increase in SIV encephalitis, TREM2 returns to baseline levels with suppressive ART. This shows that while similar, TREM2 and CSF1R have unique roles in neuroinflammation, particularly in the context of chronic, suppressed SIV infection. Finally, we performed a pilot pre-clinical drug trial in suppressed, SIV-infected pigtailed macaques with PLX3397, a small-molecule CSF1R inhibitor. PLX3397 was kept onboard after animals were released from ART. PLX3397 treatment reduced the number of microglia both in vitro and in vivo. While PLX3397 had no effect on plasma viral rebound, treatment prevented viral rebound in the cerebrospinal fluid of one animal. Additionally, PLX3397 treatment changed the morphology of the remaining microglia from an ameboid, activated state to a resting/surveilling state. The work presented in this dissertation provides a unique insight into the mechanisms of chronic inflammation in the CNS of SIV-infected pigtailed macaques lays the groundwork for future preclinical drug trials to treat HIV CNS disease

Gremlin, noggin, chordin and follistatin differentially modulate BMP induced suppression of androgen secretion by bovine ovarian theca cells

Bone morphogenetic proteins (BMP) are firmly implicated as intra-ovarian regulators of follicle function and steroidogenesis but information is lacking regarding the regulation of BMP signalling by extracellular binding proteins co-expressed in the ovary. In this study we compared the abilities of four BMP binding proteins (gremlin, noggin, chordin, follistatin) to antagonize the action of four different BMPs (BMP2 BMP4, BMP6, BMP7) on LH-induced androstenedione secretion by bovine theca cells in primary culture. Expression of the four BMP binding proteins and BMPs investigated here has previously been documented in bovine follicles. All four BMPs suppressed androstenedione secretion by >85%. Co-treatment with gremlin antagonized BMP2- and, less potently, BMP4-induced suppression of androgen secretion but did not affect responses to BMP6 and BMP7. Noggin antagonized the effects of three BMPs (rank order: BMP4 > BMP2 > BMP7) but did not affect the response to BMP6. Follistatin partially reversed the suppressive effects of BMP6 on androgen secretion but did not affect BMP2, BMP4 and BMP7 action. Chordin had no effect on the response to any of the four BMPs. BMP6 treatment upregulated thecal expression of GREM1, NOG, CHRD and SMAD6 mRNA whilst inhibiting expression of the four BMPs. Taken together with previous work documenting the intra-ovarian expression of different BMPs, BMP binding proteins and signalling receptors, these observations reinforce the conclusion that extracellular binding proteins selectively modulate BMP-dependent alterations in thecal steroidogenesis. As such they likely constitute an important regulatory component of this, and other intra-ovarian actions of BMPs

Theca cells and the regulation of ovarian androgen production

Theca cells are essential for female reproduction being the source of androgens that are precursors for follicular oestrogen synthesis and also signal through androgen receptors (AR) in the ovary and elsewhere. Theca cells arise from mesenchymal cells around the secondary follicle stage. Their recruitment, proliferation and cytodifferentiation are influenced, directly or indirectly, by paracrine signals from granulosa cells and oocyte although uncertainty remains over which are the critically important signals at particular stages. In a reciprocal manner, theca cells secrete factors that influence granulosa cell proliferation and differentiation at different follicle stages. Differentiated theca interna cells acquire responsiveness to luteinizing hormone (LH) and other endocrine signals and express components of the steroidogenic machinery required for androgen biosynthesis. They also express insulin-like peptide 3 (INSL3) and its receptor (RXFP2), levels of which increase during bovine antral follicle development. INSL3 signaling may play a role in promoting androgen biosynthesis since knockdown of either INSL3 or its receptor (RXFP2) in bovine theca cells inhibits androgen biosynthesis while exogenous INSL3 can raise androgen secretion. Bone morphogenetic proteins (BMPs) of thecal or granulosal origin suppress thecal production of both INSL3 and androgen. Inhibin, produced in greatest amounts by granulosa cells of preovulatory follicles, reverses these BMP actions. Thus, BMP-induced inhibition of thecal androgen production may be mediated by reduced INSL3-RXFP2 signaling. Activins also inhibit androgen production in an inhibin-reversible manner and recent evidence in sheep indicates that theca cells synthesize and secrete activin, implying an autocrine role in suppressing androgen biosynthesis in smaller follicles, akin to that envisaged for BMPs

The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells

Background Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating. To investigate the effects of stimulatory (follicle-stimulating hormone; FSH) and inhibitory (tumour necrosis factor alpha; TNFα) factors on the granulosa cell transcriptome, bovine ovaries were obtained from a local abattoir and pools of granulosa cells were cultured in vitro for six days under defined serum-free conditions with treatments present on days 3–6. Initially dose–response experiments (n = 4) were performed to determine the optimal concentrations of FSH (0.33 ng/ml) and TNFα (10 ng/ml) to be used for the microarray experiments. For array experiments cells were cultured under control conditions, with FSH, with TNFα, or with FSH plus TNFα (n = 4 per group) and RNA was harvested for microarray analyses. Results Statistical analysis showed primary clustering of the arrays into two groups, control/FSH and TNFα/TNFα plus FSH. The effect of TNFα on gene expression dominated that of FSH, with substantially more genes differentially regulated, and the pathways and genes regulated by TNFα being similar to those of FSH plus TNFα treatment. TNFα treatment reduced the endocrine activity of granulosa cells with reductions in expression of FST, INHA, INBA and AMH. The top-ranked canonical pathways and GO biological terms for the TNFα treatments included antigen presentation, inflammatory response and other pathways indicative of innate immune function and fibrosis. The two most significant networks also reflect this, containing molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor β signalling, and these were up regulated. Upstream regulator analyses also predicted TNF, interferons γ and β1 and interleukin 1β. Conclusions In vitro, the transcriptome of granulosa cells responded minimally to FSH compared with the response to TNFα. The response to TNFα indicated an active process akin to tissue remodelling as would occur upon atresia. Additionally there was reduction in endocrine function and induction of an inflammatory response to TNFα that displays features similar to immune cells

Measurement of volatile organic compounds emitted in libraries and archives : an inferential indicator of paper decay?

A sampling campaign of indoor air was conducted to assess the typical concentration of indoor air pollutants in 8 National Libraries and Archives across the U.K. and Ireland. At each site, two locations were chosen that contained various objects in the collection (paper, parchment, microfilm, photographic material etc.) and one location was chosen to act as a sampling reference location (placed in a corridor or entrance hallway). Of the locations surveyed, no measurable levels of sulfur dioxide were detected and low formaldehyde vapour (< 18 μg m-3) was measured throughout. Acetic and formic acids were measured in all locations with, for the most part, higher acetic acid levels in areas with objects compared to reference locations. A large variety of volatile organic compounds (VOCs) was measured in all locations, in variable concentrations, however furfural was the only VOC to be identified consistently at higher concentration in locations with paper-based collections, compared to those locations without objects. To cross-reference the sampling data with VOCs emitted directly from books, further studies were conducted to assess emissions from paper using solid phase microextraction fibres (SPME) fibres and a newly developed method of analysis; collection of VOCs onto a polydimethylsiloxane (PDMS) elastomer strip. In this study acetic acid and furfural levels were consistently higher in concentration when measured in locations which contained paper-based items. It is therefore suggested that both acetic acid and furfural (possibly also trimethylbenzenes, ethyltoluene, decane and camphor) may be present in the indoor atmosphere as a result of cellulose degradation and together may act as an inferential non-invasive marker for the deterioration of paper. Direct VOC sampling was successfully achieved using SPME fibres and analytes found in the indoor air were also identified as emissive by-products from paper. Finally a new non-invasive, method of VOC collection using PDMS strips was shown to be an effective, economical and efficient way of examining VOC emissions directly from the pages of a book and confirmed that toluene, furfural, benzaldehyde, ethylhexanol, nonanal and decanal were the most concentrated VOCs emitted directly from paper measured in this study