Synthesis of functionalised silanes for use in the asymmetric allylation reaction

Asymmetric allylation of aldehydes with allyltrichlorosilane reagents, in recent years, has become a powerful synthetic tool towards the enantioselective construction of homoallylic alcohols. In general, the reaction displays good diastereocontrol. Thus, when the allylation is carried out in the presence of a Lewis base, the homoallylic alcohols anti-3 and syn-4 are stereospecifically obtained from the (E)-2 and (Z)-2 silanes, respectively, indicating that the reaction is likely to proceed via a cyclic, chair-like transistion state. Herein, the synthesis of isomerically pure allylsilanes 2, functionalised in the γ-position is reported. This has enabled the range of valuable synthetic intermediates available via the asymmetric allylation reaction of various aromatic aldehydes to be extended. The resultant homoallylic alcohols have two new stereogenic centres. These molecules can now undergo an intramolecular SN2 reaction to afford the corresponding vinyl epoxides 5 and 6 with retention of the relative stereochemistry. A variety of chiral Lewis bases, including pyridine N-oxides and phosphine oxides, were synthesised and screened for asymmetric induction. The most notable result was achieved using chiral phosphine oxide BINAPO, which produced the syn-homoallylic alcohol 4 in 50 % ee

Making Histories and Narrating Things: Histories of Handmade Objects in Two Indigenous Communities

Building on and deepening my existing community-engaged research relationships with community members in Sliammon, B.C. and Ile-a-la-Crosse, SK, this dissertation is, as I described it to community members, a history of handmade items. At the intersection of economic change, changing colonialist policy, ideas about tradition, and Indigenous political interests that has taken place in Indigenous communities in the latter half of the twentieth century, seemingly local or domestic objects in fact highlight complexities within and beyond communities over time. The role of objects was shaped – in conflicting or paradoxical ways – by newcomer institutions that sought to define Indigenous people and their activities in constrained ways. Yet for community members, the processes and products of making things became ways to define and historicize tradition itself. These two themes – objects in families and communities, and objects in newcomer institutions – provide the overarching structure for this dissertation. People in both communities have shared in parallel processes of using and co-opting colonizing influences not only to make a living for themselves within those contexts, but also, through their involvement in “making things,” to make explicit statements about the significance of histories and historical interpretation in community changes. This dissertation, and the individual and collective experiences of making things portrayed within it, are a means of discussing how labour, gender, and tradition have been mobilized in Ile-a-la-Crosse and Sliammon in the twentieth century, and especially from the 1930s and onwards to respond to contemporary realities. Because the communities I have worked with are very different places from each other – a small, west coast First Nation and a predominantly Metis municipality in northwestern Saskatchewan – this work is intentionally not comparative. Rather, I use these two case studies to follow how community members have interpreted their histories through processes of making tangible “things,” depending on local historical circumstances. I consider the changing ways that community members have responded to and worked within colonial intervention. First and foremost, though, by making things, they sought to address their own economic, social, and political concerns. Changes in processes of making and interpreting handmade items help to illuminate how community members envisioned objects in their communities, not only as practical items or symbols of cultures or histories, but also as ways to describe the shifting significance of tradition for making sociopolitical arguments illustrated by the objects themselves

Looking for snob hill and sq’éwqel : exploring the changing histories of aboriginality and community in two aboriginal communities

This thesis explores notions of community and Aboriginality within the histories of two Aboriginal communities: the primarily Métis town of Île-à-la-Crosse, Saskatchewan and the Stó:lõ reserve of Seabird Island, British Columbia. By “reading” community members’ oral histories in terms of these two concepts, it historicises the accounts, giving temporal context to academics’ writings and local histories that at times act as snapshots of a small span of time. Considering Île-à-la-Crosse and Seabird Island in terms of their communal and Aboriginal components also complicates definitions of community and Aboriginality or indigeneity as they relate to these two places, thereby reinforcing the links between histories and the places and people from which they originated. Thus, the first part of this thesis situates Seabird Island and Île-à-la-Crosse historically and physically, and demonstrates how local oral histories introduce broader historical themes. The second part focuses on the community aspect of these places: the Aboriginal component to both Seabird Island’s and Île-à-la-Crosse’s existence is what has tended to attract outside academic research and attention, yet an Aboriginal community exists as such because of influences that make and sustain a community as well as its Aboriginal components. While each “category” draws on understandings of the other in order to create a cohesive definition of the whole, a community does not become a community simply by being Aboriginal, nor is it Aboriginal simply as a result of Aboriginal people living together. Therefore, diverse definitions and histories of Aboriginality are also significant in maintaining historical links among inhabitants of Île-à-la-Crosse and Seabird Island. There exists a historiography in these communities that, while sometimes unintentional or implicit, links community members’ accounts of their community and its Aboriginal features with outside observations. This connection places these interpretations of historical events into a historiographical context of ways these Aboriginal communities have been both, and alternately, communities and Aboriginal places

An update on nuclear calcium signalling

Over the past 15 years or so, numerous studies have sought to characterise how nuclear calcium (Ca2+) signals are generated and reversed, and to understand how events that occur in the nucleoplasm influence cellular Ca2+ activity, and vice versa. In this Commentary, we describe mechanisms of nuclear Ca2+ signalling and discuss what is known about the origin and physiological significance of nuclear Ca2+ transients. In particular, we focus on the idea that the nucleus has an autonomous Ca2+ signalling system that can generate its own Ca2+ transients that modulate processes such as gene transcription. We also discuss the role of nuclear pores and the nuclear envelope in controlling ion flux into the nucleoplasm

Plasmonic Gold Nanostars Incorporated into High-Efficiency Perovskite Solar Cells

Incorporating appropriate plasmonic nanostructures into photovoltaic (PV) systems is of great utility for enhancing photon absorption and thus improving device performance. Herein, the successful integration of plasmonic gold nanostars (AuNSs) into mesoporous TiO2 photoelectrodes for perovskite solar cells (PSCs) is reported. The PSCs fabricated with TiO2-AuNSs photoelectrodes exhibited a device efficiency of up to 17.72 %, whereas the control cells without AuNSs showed a maximum efficiency of 15.19 %. We attribute the origin of increased device performance to enhanced light absorption and suppressed charge recombination

Human chorionic gonadotropin increases β-cleavage of amyloid precursor protein in SH-SY5Y cells

Elevated levels of amyloid-β (Aβ) peptides, the main component of amyloid plaques in Alzheimer's disease, are the result of excessive β- and γ-cleavage of the amyloid precursor protein (APP) and/or impaired Aβ clearance in the brain. It has been suggested that high concentrations of luteinizing hormone (LH) in women contribute to increased Aβ generation after menopause, but the mechanism for this is incompletely understood. We investigated the effect of human chorionic gonadotropin (hCG), an LH receptor agonist, on APP β-cleavage in the SH-SY5Y neuroblastoma cell line. Treatment of these cells with hCG-induced elevated β-cleavage in a dose-dependent manner: administration of 30 mIU but not 10 mIU/ml of hCG significantly increased sAPPβ levels in the cell medium 1.7-fold as measured by ELISA. These results support the notion that LH contributes to elevated Aβ levels at least in part by increasing β-cleavage of APP by β-site APP cleaving enzyme.NHMRC grant: 104596

Rehabilitation professionals' perceptions of the use of new visualisation software tools with people with stroke

Purpose: Theenvisageprogramme of research was funded to explore and evaluate the use of visualisation software tools using biomechanical data within rehabilitation. Three work packages were developed to evaluate the impact of the tools within stroke rehabilitation. The research presented here aimed at exploring the perceptions of rehabilitation therapists about the use of the visualisation software tools in the context of future randomised controlled trials and stroke rehabilitation practice. Methods: Sixteen therapists working in a range of stroke rehabilitation contexts participated in semi-structured interviews. Interview questions explored their current practice, and the perceived impact of the new visualisation technologies on their workplace environment and practice. Framework analysis was used to analyse the textual data. Results: In general, the stroke therapists were enthusiastic about the potential application of the visualisation software tools. Three themes were identified through qualitative framework analysis: potential uses of the visualisation tools; integration within current service provision; and trial involvement. Conclusions: The study highlights important contextual considerations which may impact significantly on the success of novel technologies in stroke rehabilitation. Normalisation process theory was proposed as a useful process evaluation methodology to optimise both trial evaluation and future service implementation

Osmotic and stimulant laxatives for the management of childhood constipation

Background Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice. Objectives We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation. Search methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialized Trials Register from inception to 10 March 2016. There were no language restrictions. We also searched the references of all included studies, personal contacts and drug companies to identify studies. Selection criteria Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives to placebo or another intervention, with participants aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. Data collection and analysis Relevant papers were identified and two authors independently assessed the eligibility of trials, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. For continuous outcomes we calculated the mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated the risk ratio (RR) and 95% CI using a fixed-effect model. The Chi2 and I2 statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity. We assessed the overall quality of the evidence supporting the primary and secondary outcomes using the GRADE criteria. Main results Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95). Authors' conclusions The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation