Modulation of Angiogenesis

This invention relates to compounds, composJtwns, and methods for the treatment of traits, diseases and conditions that respond to the modulation of angiogenic growth factor bioavailability or biological activity

Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis

Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells.Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples.Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients.Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB

Theatre Vancouver

Theatres have existed throughout the human civilization as places of artistic expression and leisure. Throughout various Western cultures such as the Greek, Roman, Italian and Shakespearean etc., different theatre forms emerged. The essence of the theatre lies in the actor to audience relationship. With the invention of motion pictures, part of the theatre talent (actors, directors and technicians, etc.) switched to the motion picture industry and a further change took place with the more recent invention of television in 1927. Each industry thus created became a self-supporting form of art and the process strengthened the parent art due to competition and public demands for higher performance standards. I decided to design a theatre for Vancouver that satisfies the needs of the community. There are a number of variables that govern the design of a theatre such as: the needs of the local community as to the size and type of a theatre dictate the seating capacity and its functional usage (drama, opera, orchestra or multipurpose, etc.); economics dictate the administrative and technical structure and space-needs; and the desired actor to audience relationship dictate the stage design and seating layout. To establish a design program (space needs) a questionnaire was prepared and a number of persons connected with theatre arts were interviewed for comments and suggestions. The questions were designed to explore needs for - type of theatre, seating capacity, actor to audience relationship, orchestra size, public areas, stage design, workshop spaces, actors' accommodation, administrative organization, mechanical services and possibilities of an open-air-theatre, etc. A site for the proposed theatre was selected by establishing criteria for site selection and then testing a number of possible sites in the city against these criteria. Some of the criteria were: accessibility by car, rapid transit access, land costs, parking availability, site area, population distribution and proximity of buildings of other cultural/recreational usage and environmental setting. Out of five possible sites in the city, Vanier Park site was selected as the most appropriate site for the proposed theatre as it qualified best against the established criteria. The final proposed design has the following features: the theatre is sited towards the Music School building; public spaces such as lobbies, restaurants and lounges, etc., are directed to the best view towards -the Burrard Inlet, the downtown core and the mountains; basic actor to audience relationship has a 90 degree encirclement; seating capacity 800; stage design is a combination of proscenium stage and thrust stage with hydraulic lifts for changing scenery; a flytower over proscenium stage for flying and storing backcloths; provision for production, administrative and actor's spaces; workshops (scene shop, paint shop, metals shop and costume shop) large enough to put up a medium sized set; a projection room with light control and sound control rooms in between orchestra and balcony floors; a back stage projection room; four exits designed from each orchestra and balcony floor; stage designed with three fire-exits; technical areas designed with two fire exits and a small independent open-air-theatre for 150 seats. The only two modes of transportation - pedestrian and vehicular, have been separated from one another. Concrete is used as the primary material of construction with large span roofs of auditorium and fly-tower of steel-space-frame trusses. The sloping roofs are lined with orange coloured clay tiles. The main stage and rehearsal stage flooring is tongue and grooved Columbia-pine softwood. Orchestra and balcony floor is carpeted. A large lake is planned on the pedestrian plaza level with all elements of landscape. The proposed theatre can either be owned by the city as at present it owns a number of them or owned privately as many such ventures are running quite profitably.Applied Science, Faculty ofArchitecture and Landscape Architecture (SALA), School ofGraduat

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Porosity of bleb capsule declines rapidly with fluid challenge

Introduction: The porosity of the fibrous capsule around a glaucoma drainage device (GDD) may be the most important functional attribute. The factors that determine capsular porosity are not well understood. Failed GDD surgeries are usually associated with thick impervious capsules and components of aqueous have been implicated in this process. Purpose: In this study, we interrogated the effect of passage of nonaqueous fluid on capsular porosity in mature (but aqueous naïve) blebs in a previously reported GDD model (the Center for Eye Research Australia Implant ). Materials and methods: The study was performed at two centers using 17 New Zealand White (NZW) rabbits. An experimental GDD was implanted into the subconjunctival space but without connection to the anterior chamber. After 28 days, balanced salt solution (BSS) was passed through the implant for 30 to 40 minutes at 12 mm Hg. Capsular porosity was measured as flow (μL/min) at a constant pressure. Porosity of the capsule was retested at 3 and 6 days. Results: There was a marked reduction in capsular porosity within 3 days of exposure to BSS (fluid challenge). Even though the baseline porosity was significantly different in the two groups (3.00 ± 0.5 μL/min and 29.67 ± 12.12 μL/min, p \u3c 0.001), the effect of passage of BSS was similar. Capsular porosity fell by approximately 80% in both groups from baseline after single BSS challenge. Capsular thickness was significantly less in Advanced Eye Center (AEC) rabbits at baseline. There was no change in the capsular thickness before and after single fluid challenge. Conclusion: Passage of BSS at physiological pressures for under 40 minutes caused marked reduction in the porosity of the fibrous capsule within 3 days. This was not associated with any significant thickening of the fibrous capsule within this time frame