Metal-Induced Specific and Nonspecific Oligonucleotide Folding Studied by FRET and Related Biophysical and Bioanalytical Implications

This is the peer reviewed version of the following article: Kiy, M. M., Jacobi, Z. E., & Liu, J. (2012). Metal-Induced Specific and Nonspecific Oligonucleotide Folding Studied by FRET and Related Biophysical and Bioanalytical Implications. Chemistry - A European Journal, 18(4), 1202–1208, which has been published in final form at http://dx.doi.org/10.1002/chem.201102515 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Metal induced nucleic acid folding has been extensively studied with ribozymes, DNAzymes, tRNA and riboswitches. These RNA/DNA molecules usually have a high content of double-stranded regions to support a rigid scaffold. On the other hand, such rigid structural features are not available for many in vitro selected or rationally designed DNA aptamers; they adopt flexible random coil structures in the absence of target molecules. Upon target binding, these aptamers adaptively fold into a compact structure with a reduced end-to-end distance, making fluorescence resonance energy transfer (FRET) a popular signaling mechanism. However, nonspecific folding induced by mono- or divalent metal ions can also reduce the end-to-end distance and thus lead to false positive results. In this study we used a FRET pair labeled HgII binding DNA and monitored metal-induced folding in the presence of various cations. While nonspecific electrostatically mediated folding can be very significant, at each tested salt condition, HgII induced folding was still observed with a similar sensitivity. We also studied the biophysical meaning of the acceptor/donor fluorescence ratio that allowed us to explain the experimental observations. Potential solutions for this ionic strength problem have been discussed. For example, probes designed to signal the formation of double-stranded DNA showed a lower dependency on ionic strength.University of Waterloo || Canadian Foundation for Innovation Ontario ministry of Research and Innovation || Natural Sciences and Engineering Research Council |

The TFOS International Workshop on Contact Lens Discomfort: Executive Summary

Nichols, J. J., Willcox, M. D. P., Bron, A. J., Belmonte, C., Ciolino, J. B., Craig, J. P., … Sullivan, D. A. (2013). The TFOS International Workshop on Contact Lens Discomfort: Executive Summary. Investigative Opthalmology & Visual Science, 54(11), TFOS7. https://doi.org/10.1167/iovs.13-13212Contact lens discomfort (CLD) is a frequently experienced problem, with most estimates suggesting that up to half of contact lens wearers experience this problem with some frequency or magnitude. This condition impacts millions of contact lens wearers worldwide. Yet, there is a paucity of consensus and standardization in the scientific and clinical communities on the characterization of the condition, including the definition, classification, epidemiology, pathophysiology, diagnosis, management, influence of contact lens materials, designs and care, and the proper design of clinical trials. The Tear Film & Ocular Surface Society (TFOS), which is a nonprofit organization, has conducted two prior international, consensus building workshops, including the Dry Eye WorkShop (DEWS; available in the public domain at http://www.tearfilm.org/tearfilm-reports-dews-report.php) and the Meibomian Gland Dysfunction Workshop (MGD; available in the public domain at http://www.tearfilm.org/tearfilm-reports-mgdreport.php). To that end, TFOS initiated the process of conducting a similar workshop in January 2012—a process that took approximately 18 months to complete and included 79 experts in the field. These experts participated in one or more topical subcommittees, and were assigned with taking an evidence-based approach at evaluating CLD. Eight topical subcommittees were formed, with each generating a related report, all of which were circulated for presentation, review, and input of the entire workshop membership. The entire workshop originally is being published in this issue of IOVS, in English, with subsequent translations into numerous other languages. All of this information is intended to be available and accessible online, free of charge. This article is intended to serve as an Executive Summary of the eight subcommittee reports, and all information contained here was abstracted from the full reports

Fast assembly of non-thiolated DNA on gold surface at lower pH

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.jcis.2013.08.043 © 2013. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/In a typical protocol for attaching DNA to a gold electrode, thiolated DNA is incubated with the electrode at neutral pH overnight. Here we report fast adsorption of non-thiolated DNA oligomers on gold electrodes at acidic pH (i.e., pH ∼3.0). The peak-to-peak potential difference and the redox peak currents in typical cyclic voltammetry of [Fe(CN)6]3− are investigated to monitor the attachment. Compared with incubation at neutral pH, the lower pH can significantly promote the adsorption processes, enabling efficient adsorption even in 30 min. The adsorption rate is DNA concentration-dependent, while the ionic strength shows no influence. Moreover, the adsorption is base-discriminative, with a preferred order of A > C ≫ G, T, which is attributed to the protonation of A and C at low pH and their higher binding affinity to gold surface. The immobilized DNA is functional and can hybridize with its complementary DNA but not a random DNA. This work is promising to provide a useful time-saving strategy for DNA assembly on gold electrodes, allowing fast fabrication of DNA-based biosensors and devices.National Natural Science Foundation of China || 20905012 University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Natural Sciences and Engineering Research Council Americas Program |

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

Mohammadi, S., Jones, L., & Gorbet, M. (2014). Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models. PLoS ONE, 9(9), e106653. https://doi.org/10.1371/journal.pone.0106653In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.The funding for this project was provided by a Collaborative Health Research Project grant (jointly funded by NSERC and CIHR)

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

From McKinlay, C. J. D., Alsweiler, J. M., Ansell, J. M., Anstice, N. S., Chase, J. G., Gamble, G. D., … Harding, J. E. (2015). Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. New England Journal of Medicine, 373(16), 1507–1518. https://doi.org/10.1056/NEJMoa1504909 Copyright © 2015 Massachusetts Medical Society. Reprinted with permission.Neonatal hypoglycemia is a common and readily treatable risk factor for neurologic impairment in children. Although associations between prolonged symptomatic neonatal hypoglycemia and brain injury are well established,1 the effect of milder hypoglycemia on neurologic development is uncertain.2 Consequently, large numbers of newborns are screened and treated for low blood glucose concentrations, which involves heel-stick blood tests, substantial costs, and the possibility of iatrogenic harm. Under current guidelines,3 up to 30% of neonates are considered to be at risk for hypoglycemia, 15% receive a diagnosis of hypoglycemia, and approximately 10% require admission to a neonatal intensive care unit,4 costing an estimated $2.1 billion annually in the United States alone.5 Associated formula feeding and possible separation of mother and baby reduce breast-feeding rates,6 with potentially adverse effects on broader infant health and development. In addition, pain-induced stress in neonates, such as repeated heel sticks, may itself impair brain development.7 Thus, to determine appropriate glycemic thresholds for treatment, there have been repeated calls for studies of the effect of neonatal hypoglycemia on long-term development.2,8 We report the results of the Children with Hypoglycaemia and Their Later Development (CHYLD) study, a large prospective cohort study of term and late-preterm neonates born at risk for hypoglycemia. The study investigated the relation between the duration, frequency, and severity of low glucose concentrations in the neonatal period and neuropsychological development at 2 years.Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069622), the Health Research Council of New Zealand (10-399), and the Auckland Medical Research Foundation (1110009)

Political feasibility of 1.5°C societal transformations: the role of social justice

Constraining global climate change to 1.5°C is commonly understood to require urgent and deep societal transformations. Yet such transformations are not always viewed as politically feasible; finding ways to enhance the political feasibility of ambitious decarbonization trajectories is needed. This paper reviews the role of social justice as an organizing principle for politically feasible 1.5°C transformations. A social justice lens usefully focuses attention on first, protecting vulnerable people from climate change impacts, second, protecting people from disruptions of transformation, and finally, enhancing the process of envisioning and implementing an equitable post-carbon society. However, justice-focused arguments could also have unintended consequences, such as being deployed against climate action. Hence proactively engaging with social justice is critical in navigating 1.5°C societal transformations.INOGOV (EU COST Action ISI309)European Union, Horizon 2020 (Marie Sklodowska-Curie grant #659065

Motivational Affordance and Risk-Taking Across Decision Domains

To view the final version © 2016 by the Society for Personality and Social Psychology, Inc. SAGE publication go here: http://dx.doi.org/10.1177/0146167215626706We propose a motivational affordance account to explain both stability and variability in risk-taking propensity in major decision domains. We draw on regulatory focus theory to differentiate two types of motivation (prevention, promotion) that play a key role in predicting risk-taking. Study 1 demonstrated that prevention motivation is negatively associated with risk-taking across six key decision domains, including health/safety, ethics, recreation, gambling, investment, and social. In contrast, promotion motivation is positively associated with risk-taking in the social and investment domains. Study 2 replicated the same pattern and provided direct evidence that promotion motivation is a strong predictor of risk-taking only in domains where there is true potential for gains. Study 3 manipulated promotion (vs. prevention) motivation experimentally to demonstrate that motivational affordance is a critical mechanism for understanding risk-taking behaviors.Research and Materials Development Fund from London Business School to Xi Zo

A Web of Expectations: Evolving Relationships in Community Participatory Geoweb Projects.

This article was first published in ACME: An International Journal for Critical Geographies in 2015, available online: http://ojs.unbc.ca/index.php/acme/article/view/1235/1030.New forms of participatory online geospatial technology have the potential to support citizen engagement in governance and community development. The mechanisms of this contribution have predominantly been cast in the literature as ‘citizens as sensors’, with individuals acting as a distributed network, feeding academics or government with data. To counter this dominant perspective, we describe our shared experiences with the development of three community-based Geospatial Web 2.0 (Geoweb) projects, where community organizations were engaged as partners, with the general aim to bring about social change in their communities through technology development and implementation. Developing Geoweb tools with community organizations was a process that saw significant evolution of project expectations and relationships. As Geoweb tool development encountered the realities of technological development and implementation in a community context, this served to reduce organizational enthusiasm and support for projects as a whole. We question the power dynamics at play between university researchers and organizations, including project financing, both during development and in the long term. How researchers managed, or perpetuated, many of the popular myths of the Geoweb, namely that it is inexpensive and easy to use (thought not to build, perhaps) impacted the success of each project and the sustainability of relationships between researcher and organization. Ultimately, this research shows the continuing gap between the promise of online geospatial technology, and the realities of its implementation at the community level.Peer-reviewe

Realism in Contemporary Fine Art

The Independent Studies program closed in 2016. This thesis was one of 25 accepted by Library for long-term preservation and presentation in UWSpace.Usually I start out with a technical concept. I try to get as detailed as possible in regards to the logistics of how I'll carry out the work. The ideas themselves are quite intricate and so an intuitive approach to process isn't appropriate. Instead lots of research and a mapped out plan of action are required. I don't no longer think of art as an explorative process, except in the most general way. My approach is very exploitive. Most people think of artists as engaging in an activity that is essentially explorative, an open ended thing, the inquisitive mind journeying along uncharted creative waters. I believe this is a very narrow understanding of the process. There needs to be a managing consciousness that marshals resources and knowledge towards a desired end. The whole act of creation is a dance with chaos; where do the ideas come from in the first place? How are experience, knowledge, and history thrown together? How is the vaguest impression transformed into an actual real thing that everyone understands? How does the mind thread its way through various influences to arrive at unique conclusions? The source itself is unquantifiable; so why not rationalize as much of the process as you can? (One can never fully control it, but in trying to, one can at least come to understand it.) Of course it never does go as planned. In less than perfect attempts, one reaches a point where a decision needs to be made as to whether one should resolve a piece of art or continue trying to actualize what it was supposed to be. This was the point I reached with the Demoiselles des Avignon project on October 1 2009. I lacked the experience necessary to carry out the ambitious scheme as originally laid out, but at one point I did have an interesting and potentially successful painting. Integrity dictates that the artist sacrifice everything in pursuit of artistic truth. In this frame of reference there is no compromise, the vision must be realized (this presumes that the artist fully understands the vision at the outset, which I'm not at all sure is most often the case). However, on the ground, an artist is essentially a project manager, unlike anyone running anything, they must constantly evaluate risk versus reward. At what point do I throw the map out the window and look around? This moment hit me on October 1st, with a little over a month left and a lifetime's worth of work still to complete. The practical voice of compromise took over. I re-evaluated what I had achieved. Understanding that I could not complete this painting anytime soon I decided to scrap the methodology that I had employed over the Spring and Summer. The plan had been to produce three paintings of the same subject matter. Here's how they would have theoretically related to each other: (one) The Rubensian, baroque method would have relied largely on drawing skill, and manipulated layers of opaque/transparent paint layers to achieve a luminous sense of plasticity. (two) The modern realist painting was to rely largely on accurate colour relationships to do the heavy lifting with the drawing aspects were to be simplified to generalized shapes. (three) The third painting was going to be guided by an expressionist sensibility. It was not to rely on a particular method, but rather explore some interesting themes from the other two paintings to build up an interesting surface, one that did not rely so strictly on observation. This exercise was meant to explore the intricate relationship between aesthetic approach and subject matter, and this is where a piece succeeds or fails. It's where all the associative commentary happens- an extremely subtle, and tricky dialogue to truly understand. This cannot be so quickly mastered, through such diagramatic means (...by me...at this juncture in time). Sitting in front of me on October 1st, was a painting that resembled none of the 3 hypothetical scenarios described above. I had started one way and then lost focus, and began to rely on instincts where I couldn't solve technical problems. Thus, the work lacked the conviction of the "vision" it was meant to express. At this point I was trying to finish one painting within the remaining month. Seeing as the piece was already compromised, I then tried to hack through the remaining 20% of the painting. every desperate attempt seemed to bring me further and further away from the finish line1. At that point, I was looking at a piece that was utterly confused, and ought to be abandoned. This essay is an exploration of those issues, which I failed to do through painting

A Comprehensive Screen of Metal Oxide Nanoparticles for DNA Adsorption, Fluorescence Quenching, and Anion Discrimination

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acsami.5b08004Although DNA has been quite successful in metal cation detection, anion detectioin remains challenging because of the charge repulsion. Metal oxides represent a very important class of materials, and different oxides might interact with anions differently. In this work, a comprehensive screen of common metal oxide nanoparticles (MONPs) was carried out for their ability to adsorb DNA, quench fluorescence, and release adsorbed DNA in the presence of target anions. A total of 19 MONPs were studied, including Al2O3, CeO2, CoO, Co3O4, Cr2O3, Fe2O3, Fe3O4, In2O3, ITO, Mn2O3, NiO, SiO2, SnO2, a-TiO2 (anatase), r-TiO2 (rutile), WO3, Y2O3, ZnO, ZrO2. These MONPs have different DNA adsorption affinity. Some adsorb DNA without quenching the fluorescence, while others strongly quench adsorbed fluorophores. They also display different affinity toward anions probed by DNA desorption. Finally, CeO2, Fe3O4, and ZnO were used to form a sensor array to discriminate phosphate, arsenate, and arsenite from the rest using linear discriminant analysis. This study not only provides a solution for anion discrimination using DNA as a signaling molecule but also provides insights into the interface of metal oxides and DNA.Natural Sciences and Engineering Research Council || Discovery and Strategic Project Grant: STPGP-447472-2013 05576