A miR-433 mediated mechanism of chemoresistance in high grade serous ovarian cancer (HGSOC).

Higher expression of the miR-433 microRNA (miRNA) is associated with poorer survival outcomes in patients with HGSOC that may be overcome by a greater understanding of the functional role of this miRNA. We previously described miR-433 as a critical cell cycle regulator and mediator of cellular senescence. Downregulation of the mitotic arrest deficiency 2 (MAD2) protein by miR-433 led to increased cellular resistance to paclitaxel in epithelial ovarian cancer cells (EOC). Furthermore immunohistochemical (IHC) analysis of MAD2 expression in patients with HGSOC showed that loss of MAD2 was significantly associated with poorer patient survival. Higher miR-433 expression is also associated with an increased resistance to the platins which is unrelated to loss of MAD2 expression. In silico analysis of the miR-433 target proteins in the TCGA database identified the association between a number of miR-433 targets and poorer patient survival. IHC analysis of the miR-433 target, histone deacetylase 6 (HDAC6), confirmed that its expression was significantly associated with a decrease in patient overall survival. The knock-down of HDAC6 by siRNA in EOC cells did not attenuate apoptotic responses to paclitaxel or platin although lower endogenous HDAC6 expression was associated with more resistant EOC cell lines. In vitro analysis revealed that EOC cells which survived chemotherapeutic kill with high doses of paclitaxel expressed higher miR-433 and concomitant decreased expression of the miR-433 targets. These cells were more chemoresistant compared to the parental cell line and repopulated as 3d organoid cultures in non-adherent stem cell selective conditions; thus indicating that the cells which survive chemotherapy were viable, capable of regrowth and had an increased potential for pluripotency. In conclusion, our data suggests that chemotherapy is not driving the transcriptional upregulation of miR-433 but rather selecting a population of cells with high miR-433 expression that may contribute to chemoresistant disease and tumour recurrence.

Risk factors (excluding hormone therapy) for endometrial hyperplasia: a systematic review.

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH).

Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015.

Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories.

Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk.

Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Twentieth Century Music December 6, 1971

Concert Program for Twentieth Century Music, Dec. 6, 1971

The Tales of Hoffmann November 10, 11, 12, 13, 1988

Concert Program for The Tales of Hoffmann November 10, 11, 12, 13 1988

Cyborg Subjects: Discourses on Digital Culture

This book is an interrogation of humanity's new potentials and threats brought by technology when the question of social change is becoming more crucial than ever. Collected in the course of 2010-2012, the selected essays in this anthology confront questions from a wide-ranging perspective that evoke the postmodern idea of the cyborg to illuminate recent phenomena from global warming, Wikileaks, to the Occupy movements. Multiple disciplines from music to psychoanalysis to journalism to anthropology collaborate to examine the way we shape the world from behind our ubiquitous screens to taking to the streets in mass protests. What does the increasing omnipotence of networked machines ultimately mean? What do social networks do to our sense of self, others and society? Does P2P technology foster new ethics and spiritualities? What potentials does posthumanity have to bring about social change? Featuring essays from Robert Barry, Siri Driessen & Roos van Haaften, Bonni Rambatan, Dustin Cohen, Jacob Johanssen, Michel Bauwens, Aliki Tzatha, Zakary Paget, Stefen Baack, Alessandro Zagato, Peter Nikolaus Funke, Glenn Muschert, and Jung-Hua Liu.

Detection of ZnS phases in CZTS thin-films by EXAFS

Copper zinc tin sulfide (CZTS) is a promising Earthabundant thin-film solar cell material; it has an appropriate band gap of ~1.45 eV and a high absorption coefficient. The most efficient CZTS cells tend to be slightly Zn-rich and Cu-poor. However, growing Zn-rich CZTS films can sometimes result in phase decomposition of CZTS into ZnS and Cu2SnS3, which is generally deleterious to solar cell performance. Cubic ZnS is difficult to detect by XRD, due to a similar diffraction pattern. We hypothesize that synchrotron-based extended X-ray absorption fine structure (EXAFS), which is sensitive to local chemical environment, may be able to determine the quantity of ZnS phase in CZTS films by detecting differences in the second-nearest neighbor shell of the Zn atoms. Films of varying stoichiometries, from Zn-rich to Cu-rich (Zn-poor) were examined using the EXAFS technique. Differences in the spectra as a function of Cu/Zn ratio are detected. Linear combination analysis suggests increasing ZnS signal as the CZTS films become more Zn-rich. We demonstrate that the sensitive technique of EXAFS could be used to quantify the amount of ZnS present and provide a guide to crystal growth of highly phase pure films.

Engineers and technicians : the effect of cognitive style and gender on visual information processing

The purpose of this project was to identify in a subject group of engineers and technicians (N = 62) a preferred mode of representation for facilitating correct recall of information from complex graphics. The modes of representation were black and white (b&w) block, b&w icon, color block, and color icon. The researcher's test instrument included twelve complex graphics (six b&w and six color - three per mode). Each graphics presentation was followed by two multiple-choice questions. Recall performance was better using b&w block mode graphics and color icon mode graphics. A standardized test, the Group Embedded Figures Test (GEFT) was used to identify a cognitive style preference (field dependence). Although engineers and technicians in the sample were strongly field-independent, they were not significantly more field-independent than the normative group in the Witkin, Oltman, Raskin, and Karp study (1971). Tests were also employed to look for any significant difference in cognitive style preference due to gender. None was found. Implications from the project results for the design of visuals and their use in technical training are discussed.

Ontario Medical Association fonds, 1972-1973, 1977-1978, 1980-1982, 1984-1985

This archive contains materials relating to the Ontario Medical Association. The bulk of the materials are correspondence. A complete administrative history of the association is available from, The first 100 years : a history of the Ontario Medical Association / Glenn Sawyer, Toronto : The Association, 1980? (R15 O58 S39 1980).

A Notorial Transumpt, 1497

Govan was an ancient settlement, former burgh and now a district in Glasgow, Scotland. It is situated 2.5 miles west of Glasgow City Centre, on the south bank of the River Clyde, opposite the mouth of the River Kelvin and the district of Patrick. Archaeological evidence shows that there was a church and burial ground here as early as 600-800 AD. Numerous carved tombstones dating from 900- 1100 have been found. Govan was a village comprised of thatched cottages until well into the 19th century. It became a shipbuilding town in the early 19th century.

Dynamic Upper Leg Strength and Neuromuscular Function in Children, Adolescents and Adults

This study examined muscle strength, muscle performance, and neuromuscular function during contractions at different velocities across maturation stages and between sexes. Participants included pre-pubertal, late-pubertal and adult males and females. All completed 8 isometric and 8 isokinetic leg extensions at two different velocities. Peak torque (PT), rate of torque development (PrTD), electromechanical-day (EMD), rate of muscle activation (Q30), muscle activation efficiency and coactivation were determined. Sex, maturity, and velocity main effects were found in PT and PrTD, reflecting greater values in men, adults, and isometric contractions respectively. When values were normalized to quadriceps cross-sectional area (qCSA), there was still an increase with maturity. EMD decreased with maturity. Adults had greater activation efficiency than children. Overall, differences in muscle size and neuromuscular function failed to explain group differences in PT or PrTD. More research is needed to investigate why adults may be affected to a greater extent by increasing movement velocity.

Whose Voice Is Present?: An Examination of Power and Privilege in Service-Learning in Ontario Universities

This research paper examines themes of power and privilege that occur within service-learning as described by 3 Ontario universities on their service-learning websites. Due to size and time restrictions, this paper was able to examine only 3 Ontario universities: Brock, Wilfrid Laurier, and Lakehead. The purpose of this study is geared towards service-learning practitioners in order for the universities and students to become more self-aware of their immense place of privilege within the service-learning context. Qualitative narrative analysis research methods were employed in this purposeful sample to examine how each university’s story of service-learning reflected themes of power and privilege. The research found that each university posed a unique narrative of service-learning representing various stakeholders’ voices and presence in different ways on their website. Brock largely focuses on faculty and student voices. Laurier intentionally attempts to include all three stakeholder voices, although still favours students and the university as an audience over the community. Lakehead’s unique program includes a plethora of voices and intends much of their information for the community members, students, and the university. The implications of this research demonstrate that universities have a large amount of power and privilege, which is carried through to the students within the service-learning partnership.

Functional characterization on invertebrate and vertebrate tissues of tachykinin peptides from octopus venoms

It has been previously shown that octopus venoms contain novel tachykinin peptides that despite being isolated from an invertebrate, contain the motifs characteristic of vertebrate tachykinin peptides rather than being more like conventional invertebrate tachykinin peptides. Therefore, in this study we examined the effect of three variants of octopus venom tachykinin peptides on invertebrate and vertebrate tissues. While there were differential potencies between the three peptides, their relative effects were uniquely consistent between invertebrate and vertebrae tissue assays. The most potent form (OCT-TK-III) was not only the most anionically charged but also was the most structurally stable. These results not only reveal that the interaction of tachykinin peptides is more complex than previous structure–function theories envisioned, but also reinforce the fundamental premise that animal venoms are rich resources of novel bioactive molecules, which are useful investigational ligands and some of which may be useful as lead compounds for drug design and development.

Evaporative respiratory cooling augments pit organ thermal detection in rattlesnakes

Rattlesnakes use their facial pit organs to sense external thermal fluctuations. A temperature decrease in the heat-sensing membrane of the pit organ has the potential to enhance heat flux between their endothermic prey and the thermal sensors, affect the optimal functioning of thermal sensors in the pit membrane and reduce the formation of thermal ‘‘afterimages’’, improving thermal detection. We examined the potential for respiratory cooling to improve strike behaviour, capture, and consumption of endothermic prey in the South American rattlesnake, as behavioural indicators of thermal detection. Snakes with a higher degree of rostral cooling were more accurate during the strike, attacking warmer regions of their prey, and relocated and consumed their prey faster. These findings reveal that by cooling their pit organs, rattlesnakes increase their ability to detect endothermic prey; disabling the pit organs caused these differences to disappear. Rattlesnakes also modify the degree of rostral cooling by altering their breathing pattern in response to biologically relevant stimuli, such as a mouse odour. Our findings reveal that low humidity increases their ability to detect endothermic prey, suggesting that habitat and ambush sites election in the wild may be influenced by external humidity levels as well as temperature.

Post-hatch heat warms adult beaks: irreversible physiological plasticity in Japanese quail

Across taxa, the early rearing environment contributes to adult morphological and physiological variation. For example, in birds, environmental temperature plays a key role in shaping bill size and clinal trends across latitudinal/thermal gradients. Such patterns support the role of the bill as a thermal window and in thermal balance. It remains unknown whether bill size and thermal function are reversibly plastic. We raised Japanese quail in warm (308C) or cold (158C) environments and then at a common intermediate temperature. We predicted that birds raised in cold temperatures would develop smaller bills than warm-reared individuals, and that regulation of blood flow to the bill in response to changing temperatures would parallel the bill’s role in thermal balance. Cold-reared birds developed shorter bills, although bill size exhibited ‘catch-up’ growth once adults were placed at a common temperature. Despite having lived in a common thermal environment as adults, individuals that were initially reared in the warmth had higher bill surface temperatures than coldreared individuals, particularly under cold conditions. This suggests that blood vessel density and/or the control over blood flow in the bill retained a memory of early thermal ontogeny. We conclude that post-hatch temperature reversibly affects adult bill morphology but irreversibly influences the thermal physiological role of bills and may play an underappreciated role in avian energetics