Paper Session III-A - Space Station Freedom and the Impact of its International Aspects

In the mid-1980s, the timeframe that the Space Station Freedom Program was born, it was believed that a new dawn of international cooperative relationships for all future, large-scale manned space initiatives was also born. The Space Station Freedom would be the first such program that would characterize international partnerships where intricate and highly dependent relationships were the norm. Programs in the next decade and of the 21st century could be expected to be multi-year, multi-billion dollars and multi-national. The advantages of multiple nations cooperating toward a common goal are clear in terms of the economic realities of sharing in the high costs of research and technology programs, particularly the cost of manned space endeavors. The opportunity for nations to contribute in areas of their specific strengths would aid in pushing to the edge of technology. But there are some fundamental political and management challenges that programs such as the Space Station and future ones of this magnitude will face. Unless these challenges are understood and met head on, the success of them is uncertain

Tunable nanopatterning of conductive polymers via electrohydrodynamic lithography

[Image: see text] An increasing number of technologies require the fabrication of conductive structures on a broad range of scales and over large areas. Here, we introduce advanced yet simple electrohydrodynamic lithography (EHL) for patterning conductive polymers directly on a substrate with high fidelity. We illustrate the generality of this robust, low-cost method by structuring thin polypyrrole films via electric-field-induced instabilities, yielding well-defined conductive structures with feature sizes ranging from tens of micrometers to hundreds of nanometers. Exploitation of a conductive polymer induces free charge suppression of the field in the polymer film, paving the way for accessing scale sizes in the low submicron range. We show the feasibility of the polypyrrole-based structures for field-effect transistor devices. Controlled EHL pattering of conductive polymer structures at the micro and nano scale demonstrated in this study combined with the possibility of effectively tuning the dimensions of the tailor-made architectures might herald a route toward various submicron device applications in supercapacitors, photovoltaics, sensors, and electronic displays

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

The Defeasibility of Knowledge-How

Reductive intellectualists (e.g., Stanley & Williamson 2001; Stanley 2011a; 2011b; Brogaard 2008; 2009; 2011) hold that knowledge-how is a kind of knowledge-that. If this thesis is correct, then we should expect the defeasibility conditions for knowledge-how and knowledge-that to be uniform—viz., that the mechanisms of epistemic defeat which undermine propositional knowledge will be equally capable of imperilling knowledge-how. The goal of this paper is twofold: first, against intellectualism, we will show that knowledge-how is in fact resilient to being undermined by the very kinds of traditional (propositional) epistemic defeaters which clearly defeat the items of propositional knowledge which intellectualists identify with knowledge-how. Second, we aim to fill an important lacuna in the contemporary debate, which is to develop an alternative way in which epistemic defeat for knowledge-how could be modelled within an anti-intellectualist framework

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro-Hydrodynamic Surface Molecular Lithography

Micro- and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab-on-a-chip diagnostics. Herein, a micro- and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro-hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro- and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high-precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro- and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano-plasmonic lab-on-a-chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point-of-care detection of disease-indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost-effective micro- and nanoplatforms for accurate detection.</p

Using the Internet to Help HIV-Positive Youth

The internet is a useful medium for assisting HIV positive youth. Youth need a dedicated website to access information, services, and social support to help manage their HIV.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

Window into the mind:Advanced handheld spectroscopic eye-safe technology for point-of-care neurodiagnostic

Traumatic brain injury (TBI), a major cause of morbidity and mortality worldwide, is hard to diagnose at the point of care with patients often exhibiting no clinical symptoms. There is an urgent need for rapid point-of-care diagnostics to enable timely intervention. We have developed a technology for rapid acquisition of molecular fingerprints of TBI biochemistry to safely measure proxies for cerebral injury through the eye, providing a path toward noninvasive point-of-care neurodiagnostics using simultaneous Raman spectroscopy and fundus imaging of the neuroretina. Detection of endogenous neuromarkers in porcine eyes' posterior revealed enhancement of high-wave number bands, clearly distinguishing TBI and healthy cohorts, classified via artificial neural network algorithm for automated data interpretation. Clinically, translating into reduced specialist support, this markedly improves the speed of diagnosis. Designed as a hand-held cost-effective technology, it can allow clinicians to rapidly assess TBI at the point of care and identify long-term changes in brain biochemistry in acute or chronic neurodiseases.</p