Implicit and explicit functions in the acquisition of a phonics rule in the word recognition of learning disabled and non learning disabled students /

One group of 12 non learning disabled students and two groups of 12 learning disabled students between the ges of 10 and 12 were measured on implicit and explicit knowledge cquisition. Students in each group implicitly cquired knowledge bout I of 2 vocabulary rules. The vocabulary rules governed the pronunciation of 2 types of pseudowords. After completing the implicit acquisition phase, all groups were administered a test of implicit knowledge. The non learning disabled group and I learning disabled group were then asked to verbalize the knowledge acquired during the initial phase. This was a test of explicit knowledge. All 3 groups were then given a postlest of implicit knowledge. This tcst was a measure of the effectiveness of the employment of the verbalization technique. Results indicate that implicit knowledge capabilities for both the learning disabled and non learning disabled groups were intact. However. there were significant differences between groups on explicit knowledge capabilities. This led to the conclusion that implicit functions show little individual differences, and that explicit functions are affected by ability difference. Furthermore, the employment of the verbalization technique significantly increased POStlest scores for learning disabled students. This suggested that the use of metacognitive techniques was a beneficial learning tool for learning disabled students.

Regulation of Systemic Acquired Resistance through the Interaction of Arabidopsis thaliana Transcription factors TGAI and TGA2 with NPRI

Arabidopsis thaliana is an established model plant system for studying plantpathogen interactions. The knowledge garnered from examining the mechanism of induced disease resistance in this model system can be applied to eliminate the cost and danger associated with current means of crop protection. A specific defense pathway, known as systemic acquired resistance (SAR), involves whole plant protection from a wide variety of bacterial, viral and fungal pathogens and remains induced weeks to months after being triggered. The ability of Arabidopsis to mount SAR depends on the accumulation of salicylic acid (SA), the NPRI (non-expressor of pathogenesis related gene 1) protein and the expression of a subset of pathogenesis related (PR) genes. NPRI exerts its effect in this pathway through interaction with a closely related class of bZIP transcription factors known as TGA factors, which are named for their recognition of the cognate DNA motif TGACG. We have discovered that one of these transcription factors, TGA2, behaves as a repressor in unchallenged Arabidopsis and acts to repress NPRI-dependent activation of PRJ. TGA1, which bears moderate sequence similarity to TGA2, acts as a transcriptional activator in unchallenged Arabidopsis, however the significance of this activity is J unclear. Once SAR has been induced, TGAI and TGA2 interact with NPRI to form complexes that are capable of activating transcription. Curiously, although TGAI is capable of transactivating, the ability of the TGAI-NPRI complex to activate transcription results from a novel transactivation domain in NPRI. This transactivation domain, which depends on the oxidation of cysteines 521 and 529, is also responsible for the transactivation ability of the TGA2-NPRI complex. Although the exact mechanism preventing TGA2-NPRI interaction in unchallenged Arabidopsis is unclear, the regulation of TGAI-NPRI interaction is based on the redox status of cysteines 260 and 266 in TGAl. We determined that a glutaredoxin, which is an enzyme capable of regulating a protein's redox status, interacts with the reduced form of TGAI and this interaction results .in the glutathionylation of TGAI and a loss of interaction with NPRl. Taken together, these results expand our understanding of how TGA transcription factors and NPRI behave to regulate events and gene expression during SAR. Furthermore, the regulation of the behavior of both TGAI and NPRI by their redox status and the involvement of a glutaredoxin in modulating TGAI-NPRI interaction suggests the redox regulation of proteins is a general mechanism implemented in SAR.

Multinational drug corporations, intellectual property rights and the Canadian state : a historical and critical analysis

This study critically analyzes the historical role and influence of multinational drug cotpOrations and multinational corporations in general; the u.s. government and the Canadian state in negotiating the global recognition ofIntellectual Property Rights (IPR) under GATT/NAFTA. This process began in 1969 when the Liberal government, in response to high prices for brand-name drugs amended the Patent Act to introduce compulsory licensing by reducing monopoly protection from 20 to seven years. Although the financial position ofthe multinational drug industry was not affected, it campaigned vigorously to change the 1969 legislation. In 1987, the Patent Act was amended to extend protection to 10 years as a condition for free trade talks with the u.s. Nonetheless, the drug industry was not satisfied and accused Canada of providing a bad example to other nations. Therefore, it continued to campaign for global recognition ofIPR laws under GATT. Following the conclusion of the GATTI Trade-Related aspects of Intellectual Property Rights agreement (TRIPS) in 1991, the multinational drug industry and the American government, to the surprise of many, were still not satisfied and sought to implement harsher conditions under NAFTA. The Progressive Conservative government readily agreed without any objections or consideration for the social consequences. As a result, Bill C-91 was introduced. It abandoned compulsory licenses and was made retroactive from December 21, 1991. It is the contention of this thesis that the economic survival of multinational corporations on a global scale depends on the role and functions of the modem state. Similarly, the existence of the state depends on the ideological-political and socioeconomic assistance it gives to multinational corporations on a national and international scale. This dialectical relation of the state and multinational corporations is explored in our theoretical and historical analysis of their role in public policy.

Primary structure and expression studies of the dihydrofolate reductase gene (DFRI) of Saccharomyces cerevisiae

The nucleotide sequence of a genomic DNA fragment thought previously to contain the dihydrofolate reductase gene (DFR1) of Saccharomyces cerevisiae by genetic criteria was determined. This DNA fragment of 1784' basepairs contains a large open reading frame from position 800 to 1432, which encodes a enzyme with a predicted molecular weight of 24,229.8 Daltons. Analysis of the amino acid sequence of this protein revealed that the yeast polypep·tide contained 211 amino acids, compared to the 186 residues commonly found in the polypeptides of other eukaryotes. The difference in size of the gene product can be attributed mainly to an insert in the yeast gene. Within this region, several consensus sequences required for processing of yeast nuclear and class II mitochondrial introns were identified, but appear not sufficient for the RNA splicing. The primary structure of the yeast DHFR protein has considerable sequence homology with analogous polypeptides from other organisms, especially in the consensus residues involved in cofactor and/or inhibitor binding. Analysis of the nucleotide sequence also revealed the presence of a number of canonical sequences identified in yeast as having some function in the regulation of gene expression. These include UAS elements (TGACTC) required for tIle amino acid general control response, and "TATA H boxes as well as several consensus sequences thought to be required for transcriptional termination and polyadenylation. Analysis of the codon usage of the yeast DFRl coding region revealed a codon bias index of 0.0083. this valve very close to zero suggestes 3 that the gene is expressed at a relatively low level under normal physiological conditions. The information concerning the organization of the DFRl were used to construct a variety of fusions of its 5' regulatory region with the coding region of the lacZ gene of E. coli. Some of such fused genes encoded a fusion product that expressed in E.coli and/or in yeast under the control of the 5' regulatory elements of the DFR1. Further studies with these fusion constructions revealed that the beta-galactosidase activity encoded on multicopy plasmids was stimulated transiently by prior exposure of yeast host cells to UV light. This suggests that the yeast PFRl gene is indu.ced by UV light and nlay in1ply a novel function of DHFR protein in the cellular responses to DNA damage. Another novel f~ature of yeast DHFR was revealed during preliminary studies of a diploid strain containing a heterozygous DFRl null allele. The strain was constructed by insertion of a URA3 gene within the coding region of DFR1. Sporulation of this diploid revealed that meiotic products segregated 2:0 for uracil prototrophy when spore clones were germinated on medium supplemented with 5-formyltetrahydrofolate (folinic acid). This finding suggests that, in addition to its catalytic activity, the DFRl gene product nlay play some role in the anabolisln of folinic acid. Alternatively, this result may indicate that Ura+ haploid segregants were inviable and suggest that the enzyme has an essential cellular function in this species.

The role of water in determining structure and function of macromolecules and macromolecular assemblies /

The interaction of biological molecules with water is an important determinant of structural properties both in molecular assemblies, and in conformation of individual macromolecules. By observing the effects of manipulating the activity of water (which can be accomplished by limiting its concentration or by adding additional solutes, "osmotic stress"), one can learn something about intrinsic physical properties of biological molecules as well as measure an energetic contribution of closely associated water molecules to overall equilibria in biological reactions. Here two such studies are reported. The first of these examines several species of lysolipid which, while present in relatively low concentrations in biomembranes, have been shown to affect many cellular processes involving membrane-protein or membrane-membrane interactions. Monolayer elastic constants were determined by combining X-ray diffraction and the osmotic stress technique. Spontaneous radii of curvature of lysophosphatidylcholines were determined to be positive and in the range +30A to +70A, while lysophosphatidylethanolamines proved to be essentially flat. Neither lysolipid significantly affected the bending modulus of the monolayer in which it was incorporated. The second study examines the role of water in theprocess of polymerization of actin into filaments. Water activity was manipulated by adding osmolytes and the effect on the equilibrium dissociation constant (measured as the criticalmonomer concentration) was determined. As water activity was decreased, the critical concentration was reduced for Ca-actin but not for Mg-actin, suggesting that 10-12 fewer water molecules are associated with Ca-actin in the polymerized state. Thisunexpectedly small amount of water is discussed in the context of the common structural motif of a nucleotide binding cleft.

Reliability of muscle fiber conduction velocity in the tibialis anterior

This document could not have been completed without the hard work of a number of individuals. First and foremost, my supervisor, Dr. David Gabriel deserves the utmost recognition for the immense effort and time spent guiding the production of this document through the various stages of completion. Also, aiding in the data collection, technical support, and general thought processing were Lab Technician Greig Inglis and fellow members of the Electromyographic Kinesiology Laboratory Jon Howard, Sean Lenhardt, Lara Robbins, and Corrine Davies-Schinkel. The input of Drs. Ted Clancy, Phil Sullivan and external examiner Dr. Anita Christie, all members ofthe assessment committee, was incredibly important and vital to the completion of this work. Their expertise provided a strong source of knowledge and went to ensure that this project was completed at exemplary level. There were a number of other individuals who were an immense help in getting this project off the ground and completed. The donation of their time and efforts was very generous and much needed in order to fulfill the requirements needed for completion of this study. Finally, I cannot exclude the contributions of my family throughout this project especially that of my parents whose support never wavers.

Electrophysiological investigations of the timing of face processing

As important social stimuli, faces playa critical role in our lives. Much of our interaction with other people depends on our ability to recognize faces accurately. It has been proposed that face processing consists of different stages and interacts with other systems (Bruce & Young, 1986). At a perceptual level, the initial two stages, namely structural encoding and face recognition, are particularly relevant and are the focus of this dissertation. Event-related potentials (ERPs) are averaged EEG signals time-locked to a particular event (such as the presentation of a face). With their excellent temporal resolution, ERPs can provide important timing information about neural processes. Previous research has identified several ERP components that are especially related to face processing, including the N 170, the P2 and the N250. Their nature with respect to the stages of face processing is still unclear, and is examined in Studies 1 and 2. In Study 1, participants made gender decisions on a large set of female faces interspersed with a few male faces. The ERP responses to facial characteristics of the female faces indicated that the N 170 amplitude from each side of the head was affected by information from eye region and by facial layout: the right N 170 was affected by eye color and by face width, while the left N 170 was affected by eye size and by the relation between the sizes of the top and bottom parts of a face. In contrast, the P100 and the N250 components were largely unaffected by facial characteristics. These results thus provided direct evidence for the link between the N 170 and structural encoding of faces. In Study 2, focusing on the face recognition stage, we manipulated face identity strength by morphing individual faces to an "average" face. Participants performed a face identification task. The effect of face identity strength was found on the late P2 and the N250 components: as identity strength decreased from an individual face to the "average" face, the late P2 increased and the N250 decreased. In contrast, the P100, the N170 and the early P2 components were not affected by face identity strength. These results suggest that face recognition occurs after 200 ms, but not earlier. Finally, because faces are often associated with social information, we investigated in Study 3 how group membership might affect ERP responses to faces. After participants learned in- and out-group memberships of the face stimuli based on arbitrarily assigned nationality and university affiliation, we found that the N170 latency differentiated in-group and out-group faces, taking longer to process the latter. In comparison, without group memberships, there was no difference in N170 latency among the faces. This dissertation provides evidence that at a neural level, structural encoding of faces, indexed by the N170, occurs within 200 ms. Face recognition, indexed by the late P2 and the N250, occurs shortly afterwards between 200 and 300 ms. Social cognitive factors can also influence face processing. The effect is already evident as early as 130-200 ms at the structural encoding stage.

The Clinical Translation Gap in Child Health Exercise Research: A Call for Disruptive Innovation

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the child health spectrum.

Can poor readers visually recognize words they are unable to read? /

The ability to learn new reading vocabulary was assessed in 30 grade 3 poor readers reading approximately one to two years below grade level; the results of the assessment were compared to the performance abilities of 33 normal readers in grade 3 as obtained from an earlier study that employed the same approach and stimuli. The purpose of the study was to examine the strategies employed by poor readers in the acquisition of new reading vocabulary. Students were randomly assigned to either a treatment group (Mixed Phonics Explicit), or to a control group (Phonics Implicit). Subjects in the Mixed Phonics Explicit groups received explicit letter/sound correspondence training. Subjects in the Phonics Implicit group were asked to re-read the presented pseudo-words, receiving corrective feedback when necessary. The stimuli on which the subjects were trained involved a list of six pseudo-words presented in sentences as surnames. The training involved a teaching and test format on each trial for a total of six trials or until criterion had been reached. The results suggested that both normal and poor readers engage in visual learning and verbal coding when acquiring new reading vocabulary. However, poor readers appear to engage in less verbal coding than normal readers. Between group comparisons showed no difference between poor and normal readers in trials and errors to criterion in the visual recognition memory measure. However, normal readers performed significantly better in reading their visual recognition choices.

Isolation and partial characterization of host cell wall surface glycoproteins: their involvement in agglutination, attachment and appressorium formation by piptocephalis virginiana

Cell surface proteins obtained by alkaline extraction from isolated cell walls of Mortierella pusilla and M. candelabrum, host and nonhost, respectively, to the mycoparasite, Piptocephalis virginiana, were tested for their ability to agglutinate mycoparasite spores. The host cell wall protein extract had a high agglutinating activity (788 a.u. mg- t ) as compared with the nonhost extract (21 a.li. mg- t ). SDS-polyacrylamide gel electrophoresis of the cell wall proteins revealed four protein bands, a, b, c, and d (Mr 117, 100, 85 and 64 kd, respectively) at the host surface, but not at the nonhost surface, except for the faint band c. Deletion of proteins b or c from the host cell wall protein extract significantly reduced its agglutinating activity. Proteins band c, obtained as purified preparations by a series of procedures, were shown to be two glycoproteins. Carbohydrate analysis by gas chromatography demonstrated that glucose and Nacetylglucosamine were the major carbohydrate components of the glycoproteins. It was further shown that the agglutinating activity of the pure preparation containing both band c was 500-850 times that of the single glycoproteins, suggesting the involvement of both glycoproteins in agglutination. The results suggest that the glycoproteins band c are the two subunits of agglutinin present at the host cell surface. The two glycoproteins band c purified from the host cell wall protein extract were further examined after various treatments for their possible role in agglutination, attachment and appressorium formation by the mycoparasite. Results obtained by agglutination and attachment tests showed: (1) the two glycoprotein-s are not only an agglutinin responsible for the mycoparasite spore agglutination, but may also serve as a receptor for the specific recognition, attachment and appressorium formation by the mycoparasite; (2) treatment of the rnycoparasite spores with various sugars revealed that arabinose, glucose and N-acetylglucosamine inhibited the agglutination and attachment activity of the glycoproteins, however, the relative percentage of appressorium formation was not affected by the above sugars; (3) the two glycoproteins are relatively stable with respect to their agglutinin and receptor functions. The present results suggest that the agglutination and attachment may be mediated directly by certain sugars present at the host and mycoparasite cell surfaces while the appressorlum formation may be the response of complementary combinations of both sugar and protein, the two parts of the glycoproteins at the interacting surfaces of two fungi.

DNA-Directed DNA Polymerases Evolve From Reverse Transcriptase

Scientists have been debating for decades the origin of life on earth. A number of hypotheses were proposed as to what emerged first RNA or DNA; with most scientists are in favour of the "RNA World" hypothesis. Assuming RNA emerged first, it fellow that the RNA polymerases would've appeared before DNA polymerases. Using recombinant DNA technology and bioinformatics we undertook this study to explore the relationship between RNA polymerases, reverse transcriptase and DNA polymerases. The working hypothesis is that DNA polymerases evolved from reverse transcriptase and the latter evolved from RNA polymerases. If this hypothesis is correct then one would expect to find various ancient DNA polymerases with varying level of reverse transcriptase activity. In the first phase of this research project multiple sequence alignments were made on the protein sequence of 32 prokaryotic DNA-directed DNA polymerases originating from 11 prokaryotic families against 3 viral reverse transcriptase. The data from such alignments was not very conclusive. DNA polymerases with higher level of reverse transcriptase activity were non-confined to ancient organisms, as one would've expected. The second phase of this project was focused on conditions that may alter the DNA polymerase activity. Various reaction conditions, such as temperature, using various ions (Ni2+, Mn2+, Mg2+) were tested. Interestingly, it was found that the DNA polymerase from the Thermos aquatics family can be made to copy RNA into DNA (i.e. reverse transcriptase activity). Thus it was shown that under appropriate conditions (ions and reactions temperatures) reverse transcriptase activity can be induced in DNA polymerase. In the third phase of this study recombinant DNA technology was used to generate a chimeric DNA polymerase; in attempts to identify the region(s) of the polymerase responsible for RNA-directed DNA polymerase activity. The two DNA polymerases employed were the Thermus aquatic us and Thermus thermophiles. As in the second phase various reaction conditions were investigated. Data indicated that the newly engineered chimeric DNA polymerase can be induced to copy RNA into DNA. Thus the intrinsic reverse transcriptase activity found in ancient DNA polymerases was localized into a domain and can be induced via appropriate reaction conditions.