Difficulties Encountered in Projecting Canada’s Aboriginal Population

Abstract not availabl

The potential for circular dichroism as an additional facile and sensitive method of monitoring low-molecular-weight heparins and heparinoids

The ultraviolet circular dichroism (CD) spectra of commercial low-molecular-weight heparins, heparinoids and other anticoagulant preparations have been recorded between 180 and 260 nm. Principal component analysis of the spectra allowed their differentiation into a number of groups related to the means of their production reflecting the structural changes introduced by each process. The findings suggest that CD provides a complementary technique for the rapid analysis of heparin preparations

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “Shotgun” Ion Mobility Mass Spectrometry Sequencing (SIMMS2) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3O-sulfate groups. SIMMS2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation

Learning, Social Intelligence and the Turing Test - why an "out-of-the-box" Turing Machine will not pass the Turing Test

The Turing Test (TT) checks for human intelligence, rather than any putative general intelligence. It involves repeated interaction requiring learning in the form of adaption to the human conversation partner. It is a macro-level post-hoc test in contrast to the definition of a Turing Machine (TM), which is a prior micro-level definition. This raises the question of whether learning is just another computational process, i.e. can be implemented as a TM. Here we argue that learning or adaption is fundamentally different from computation, though it does involve processes that can be seen as computations. To illustrate this difference we compare (a) designing a TM and (b) learning a TM, defining them for the purpose of the argument. We show that there is a well-defined sequence of problems which are not effectively designable but are learnable, in the form of the bounded halting problem. Some characteristics of human intelligence are reviewed including it's: interactive nature, learning abilities, imitative tendencies, linguistic ability and context-dependency. A story that explains some of these is the Social Intelligence Hypothesis. If this is broadly correct, this points to the necessity of a considerable period of acculturation (social learning in context) if an artificial intelligence is to pass the TT. Whilst it is always possible to 'compile' the results of learning into a TM, this would not be a designed TM and would not be able to continually adapt (pass future TTs). We conclude three things, namely that: a purely "designed" TM will never pass the TT; that there is no such thing as a general intelligence since it necessary involves learning; and that learning/adaption and computation should be clearly distinguished.Comment: 10 pages, invited talk at Turing Centenary Conference CiE 2012, special session on "The Turing Test and Thinking Machines

Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans

Tsetse flies are the principal insect vectors of African trypanosomes—sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides. Owing to the technical challenges of detecting small amounts of GAG polysaccharides, their conclusive identification and composition have not been possible until now. Following removal of PMs from the insects and the application of heparinases (bacterial lyase enzymes that are specific for heparan sulphate (HS) GAG polysaccharides), dot blots with a HS-specific antibody showed heparan sulphate proteoglycans (HSPGs) to be present, consistent with Glossina morsitans morsitans genome analysis, as well as the likely expression of the HSPGs syndecan and perlecan. Exhaustive HS digestion with heparinases, fluorescent labeling of the resulting disaccharides with BODIPY fluorophore, and separation by strong anion exchange chromatography then demonstrated the presence of HS for the first time and provided the disaccharide composition. There were no significant differences in the type of disaccharide species present between genders or between ages (24 vs. 48 h post emergence), although the HS from female flies was more heavily sulphated overall. Significant differences, which may relate to differences in infection between genders or ages, were evident, however, in overall levels of 2-O-sulphation between sexes and, for females, between 24 and 48 h post-emergence, implying a change in expression or activity for the 2-O-sulphotransferase enzyme. The presence of significant quantities of disaccharides containing the monosaccharide GlcNAc6S contrasts with previous findings in Drosophila melanogaster and suggests subtle differences in HS fine structure between species of the Diptera

The psychological effects of terrorism are moderated by cultural worldviews

Terrorism cannot be easily studied experimentally for obvious reasons. We report the results of a laboratory study (N = 149) testing the effect of cultural worldviews on feelings of threat and hostility toward Muslims in France that include in the design the deadly terrorist attack of January 7th 2015 in Paris as a naturally occurring independent variable. The results replicate past research by showing that in a natural context, people felt more threatened and more hostile toward Muslims after the terrorist attack than before. However, the reverse occurred in an experimental condition that made the French cultural worldview of colorblind equality salient: People felt less threatened and less hostile after the terrorist attack than before. These results provide, for the first time in the context of a real terrorist attack, support for Terror Management Theory's proposal that cultural worldviews are an effective buffer against terror

Versatile Separation and Analysis of Heparan Sulfate Oligosaccharides Using Graphitized Carbon Liquid Chromatography and Electrospray Mass Spectrometry.

Heparin and heparan sulfate (HS) by nature contain multiple isomeric structures, which are fundamental for the regulation of biological processes. Here we report the use of a porous graphitized carbon (PGC) LC-MS method with effective separation and sensitivity to separate mixtures of digested HS oligosaccharides. Application of this method allowed the separation of oligosaccharide mixtures with various degree of polymerization (dp) ranging from dp4 to dp8, two dp4 isomers that were baseline resolved, four dp6 isomers, and the observation of a dp3 oligosaccharide. PGC LC-MS of complex mixtures demonstrated that compounds eluted from the column in decreasing order of hydrophilicity, with the more highly sulfated structures eluting first. Our data indicate that sulfation levels, chain length, and conformation all effect elution order. We found that PGC's resolving capabilities for the dp4 and dp6 isomeric structures makes this methodology particularly useful for the sequencing of HS saccharides, because the lack of contaminating isomeric structures provides unambiguous structural assignments from the MS/MS data. Collectively this work demonstrates that PGC column-based methods are powerful tools for enhanced separation and analysis of heterogeneous mixtures of HS saccharide species

Co-constructing Simulations with Learners: Roles, Responsibilities, and Impact

Co-constructed simulations were designed and piloted with senior occupational therapy master’s students in a neurorehabilitation practice module. The instructor served as the guide for the students through all phases of the case creation, simulation development, delivery, and debrief. The instructor facilitation promoted self-regulated learning (SRL) of knowledge and skill development through independent discovery and peer learning. This paper provides an evidence-informed co-construction simulation design with outlined stages, roles, and responsibilities for the instructor and learner. Thematic qualitative analysis of student feedback highlighted enhanced insight and SRL as a result of multiple role preparation, observation and interaction with peers, close interaction with the instructor, and the multi-stage debrief process. Recommended key features and critical interactions for a successful co-constructed design are also identified for the learner, instructor, and simulation. The co-construction simulation process and design elements are suitable for learners in any health-related field of study

Building generic anatomical models using virtual model cutting and iterative registration

Article deposited according to publisher policy posted on SHERPA/RoMEO, 30/07/2010.YesFunding provided by the Open Access Authors Fund

2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline

Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread