ESI-MS[n] of anticancer pt[iv] organoamido complexes and their interactions with DNA-model compounds /

The general solution behaviour and" the major fragmentation pathways of the anticanceractive PtIV coordination complexes, trans, trans, cis, cis-[PtCIOH{N(pFC6F4) CH2h(pY)2] (1), trans, cis, cis-[Pt(OH)2{N(p-FC6F4)CH2h(Py)2] (2), trans, cis, cis-[Pt(OH)2{N(p-HC6F4)CH2h(Py)2] (3), trans, trans, cis, cis-[PtCIOH{N(pHC6F4) CH2h(Py)2] (4), and trans, trans, cis, cis-[PtOH(OCH3){N(p-HC6F4)CH2h(PY)2] (5) (Py = pyridine) have been deduced by positive-ion tandem-in-time ESI-MS. Overall, the acquired full-scan, positive-ion ESI-MS spectra of 2, 3, and 5 were characterized by the presence of relatively low-intensity [M+Nar and [M+Kt mass spectral peaks, whereas those of 1 and 4 were dominated by extremely intense [M+Hr peaks. Complexes 2 and 3 were also noted to form [2M+Ht and [2M+Nat dilneric cations. The source of Na + and K+ ions is believed to be the sample, the solvent systems used or the transport line carrying the sample solutions into the ES ion source. Further, the fragmentation pathway of all complexes studied was found to be almost identical with concurrent loss of py and H20 molecules, loss of a {N(p-YC6F4)CH2} (Y = F, H) group and/or concomitant release of the latter group and a py ligand being the most conunon. The photochemical degradation behaviour of 1 and 2 was also investigated using either fluorescent or ultraviolet light and some products of that degradation were positively identified. Altogether, light irradiation of solutions of both complexes resulted in cation cationisation, reductive-elimination, ligand-release, ligand-exchange and ligand-addition reactions. Finally, positive- and negative-ion ESI-MSn spectra of 5' -GMP, guanosine, inosine and products of their reactions with 1, 2,3, and 4 were also recorded. On the whole, full-scan ESI-MS spectra of the pure nucleobases revealed the presence of cationic and anionic species that are highly reflective of both their solution ionic composition and their propensity t9 form polymeric clusters. Analyses of mass spectra acquired from their reaction solutions with the aforementioned platinum complexes indicated very slow kinetics. However, all complexes investigated formed, to various degrees, Pt-nucleobase adducts with guanosine and inosine, but not with 5'-GMP. The products included species having coordination numbers of III, IV, V, and VI, among which the first-time· observed, coordinatively saturated, jive-coordinate PtlI-nucleobase complexes were of most interest. The latter complexes are presumably stabilized by 7tback- donation involving the filled d orbitals of the PtII centre and the empty pz· orbital of MeCN. All products, whose peaks appeared inlull-scan ESI-MS spectra, are believed to represent solution species rather than artifacts of gas-phase processes. Finally, negativeion ESI-MSn spectra recorded in reaction solutions of 1 and 4 with guanosine and of the latter complex with inosine revealed the negative-ion-ESI-MS first-time observed, noncovalent, nucleoside-chloride adducts, with the source of chloride anion being complexes 1 and 4 theillselves. In contrast, no such adducts were observed to form with Na25'-GMP or its protonated fonn. Few suggestions are offered for the possible cause(s) behind the absence of such adduct ions.

The role of skeletal muscle PLIN proteins at rest and following lipolytic stimulation

This thesis investigated the subcellular location of skeletal muscle PLIN proteins (PLIN2, PLIN3, and PLIN5) as well as protein interactions with ATGL and HSL at rest and following lipolytic stimulation. In addition, the serine phosphorylation state of PLIN2, PLIN3, and PLIN5 was determined at rest and following lipolytic stimulation. An isolated whole muscle technique was used to study the effects of contraction and epinephrine-induced lipolysis. This method allowed for the examination of the effects of contraction and epinephrine alone and in combination. Further, the soleus was chosen for investigating the role of PLIN proteins in skeletal muscle lipolysis due to its suitability for isolated incubation, and the fact that it is primarily oxidative in nature (~80% type I fibres). It has also been previously shown to have the greatest reliance on lipid metabolism and for this reason is ideal for investigating the role of PLIN proteins in lipolysis. Immunofluorescence microscopy revealed that skeletal muscle lipid droplets are partially co-localized to both PLIN2 and PLIN5 and that contraction does not affect the amount of colocalization, indicating that PLIN5 is not recruited to lipid droplets with contraction (PLIN2 ~65%; PLIN5 ~56%). Results from the immunoprecipitation studies revealed that with lipolysis in skeletal muscle the interaction between ATGL and CGI-58 is increased (study 2: 128% with contraction, p<0.05; study 3: 50% with contraction, 25% epinephrine, 80% contraction + epinephrine, p>0.05). Further PLIN2, PLIN3, and PLIN5 all interact with ATGL and HSL, while only PLIN3 and PLIN5 interact with CGI-58. Among these interactions, the association between PLIN2 and ATGL decreases with lipolytic stimulation (study 2: 21% with contraction, p<0.05). Finally our results demonstrate that PLIN3 and PLIN5 are serine phosphorylated at rest and that the level of phosphorylation remains unchanged in the face of either contractile or adrenergic stimulation. In summary, the regulation of skeletal muscle lipolysis is a complex process involving multiple proteins and enzymes. The skeletal muscle PLIN proteins likely play a role in skeletal muscle lipid droplet dynamics, and the data from this thesis indicate that these proteins may work together in regulating lipolysis by interaction with both ATGL and HSL.

Two Levels of Motivation and Two Types of Well-Being: Relations Between General and Goal-Specific Motivations, and Eudaimonic and Hedonic Well-Being

In this thesis I assess the individual and joint predictive associations and effects between multiple motivation and well-being concepts. In particular, three pairs of motivation concepts (intrinsic/extrinsic, approach/avoidance, and eudaimonic/hedonic) are assessed simultaneously at two levels of analysis (disposition and goal) and examined in relation to two types of well-being (eudaimonic and hedonic) in two studies, one correlational and the other experimental. Study 1: Using a correlational design, participants (N = 325, M age = 19.10, 87% female) completed self-report measures assessing six motivation and two well-being concepts. Exploratory factor analyses were used to assess patterns of associations among the motivational constructs. Results indicated that constructs displaying conceptual and empirical similarities co-occur, particularly, intrinsic, approach and eudaimonic motivation. Regression models were used to assess predictive relations between the motivational constructs and well-being. Both types of well-being were predicted by approach and avoidance dispositions, and hedonic goals. Additionally, eudaimonic well-being was uniquely predicted by eudaimonic dispositions and goals, and intrinsic dispositions; and hedonic well-being was uniquely predicted by extrinsic dispositions and approach goals. The patterns of associations among motivational constructs, and similarities and differences in the ways they predict each type of well-being, are discussed. Study 2: Using an experimental design, participants (N = 447, M age = 19.30, 88% female) were randomly assigned to one of eight experimental conditions, each involving a manipulation aimed at priming combinations of the three pairs of motivational constructs at the goal level. Participants then completed measures of both types of well-being. ANOVAs were used to assess the main effects and interactions of experimental condition for each of the three pairs of motivational constructs on well-being. Main effects of experimental conditions were non-significant. However, results indicated that focus on each of the three pairs of motivational constructs predicted well-being and that the manipulation impacted well-being indirectly, through experimentally-shifted motivational focus. Few interactions emerged. Implications for future experimental research and the conceptual integration of motivation and well-being constructs are discussed. In conclusion, Studies 1 and 2 inform the motivation and well-being fields in novel ways and provide preliminary steps towards studying these fields from an integrated and comprehensive motivational framework.

Emergence of normative beliefs legitimizing antisocial behaviour in adolescents : the roles of monitoring, attachment, and temperament /

Beliefs about the rightness or wrongness of engaging in various antisocial acts, referred to here as nonnative beliefs legitimizing antisocial behaviour (nblab), have been shown to playa role in the emergence oflater antisocial behaviour. The current study represented an attempt to understand whether parental monitoring and parent-child attachment have differential relationships with these antisocial nonnative beliefs in adolescents of different temperaments. The participants, 7135 adolescents in 25 high schools (ages 10- 18 years, M = 15.7) completed a wide-ranging questionnaire as part of the broad Youth Lifestyle Choices - Community University Research Alliance project, whose goal is to identify and describe the major developmental pathways of risk behaviours and resilience in youth. Two aspects of monitoring (monitoring knowledge and surveillance/tracking), attachment security, and two measures of temperament (activity level and approach) were examined for main effects and in interactions as predictors of adolescent nonnative beliefs. All of these measures were based on adolescent self-ratings on either 3- or 4-point Likert-type scales. Several important results emerged from the study. Males were higher than females in nblab; parental monitoring knowledge and adolescent attachment security were negatively related to nblab; and temperamental activity level was positively related. Monitoring knowledge, the strongest of the predictors, was much more strongly related to nonnative beliefs than was parental surveillance/tracking, supporting the contention that it is how much parents actually know, and not their surveillance efforts, that predict adolescent nonnative beliefs. A surprising finding that is of the utmost importance was that, although several of the interactions tested were significant, none were considered to be of a meaningful magnitude (defined as sr^ > .01). The current study supported the suggestion that normative beliefs legitimizing antisocial behaviour are multiply determined, and the results were discussed with respect to the observed differential relations of parental monitoring, parent-child attachment, temperament, age, and gender to antisocial normative beliefs in adolescents. Also discussed were the need to test other parenting, temperament, and other variables that may be involved in the development of nblab; the need to directly test possible mechanisms explaining the links among the variables; and the usefulness of longitudinal research in determining possible directions of causality and developmental changes in the relationships.

Predicting performance on fluid intelligence from speed of processing, working memory, and controlled attention

Fluid inteliigence has been defined as an innate ability to reason which is measured commonly by the Raven's Progressive Matrices (RPM). Individual differences in fluid intelligence are currently explained by the Cascade model (Fry & Hale, 1996) and the Controlled Attention hypothesis (Engle, Kane, & Tuholski, 1999; Kane & Engle, 2002). The first theory is based on a complex relation among age, speed, and working memory which is described as a Cascade. The alternative to this theory, the Controlled Attention hypothesis, is based on the proposition that it is the executive attention component of working memory that explains performance on fluid intelligence tests. The first goal of this study was to examine whether the Cascade model is consistent within the visuo-spatial and verbal-numerical modalities. The second goal was to examine whether the executive attention component ofworking memory accounts for the relation between working memory and fluid intelligence. Two hundred and six undergraduate students between the ages of 18 and 28 completed a battery of cognitive tests selected to measure processing speed, working memory, and controlled attention which were selected from two cognitive modalities, verbalnumerical and visuo-spatial. These were used to predict performance on two standard measures of fluid intelligence: the Raven's Progressive Matrices (RPM) and the Shipley Institute of Living Scales (SILS) subtests. Multiple regression and Structural Equation Modeling (SEM) were used to test the Cascade model and to determine the independent and joint effects of controlled attention and working memory on general fluid intelligence. Among the processing speed measures only spatial scan was related to the RPM. No other significant relations were observed between processing speed and fluid intelligence. As 1 a construct, working memory was related to the fluid intelligence tests. Consistent with the predictions for the RPM there was support for the Cascade model within the visuo-spatial modality but not within the verbal-numerical modality. There was no support for the Cascade model with respect to the SILS tests. SEM revealed that there was a direct path between controlled attention and RPM and between working memory and RPM. However, a significant path between set switching and RPM explained the relation between controlled attention and RPM. The prediction that controlled attention mediated the relation between working memory and RPM was therefore not supported. The findings support the view that the Cascade model may not adequately explain individual differences in fluid intelligence and this may be due to the differential relations observed between working memory and fluid intelligence across different modalities. The findings also show that working memory is not a domain-general construct and as a result its relation with fluid intelligence may be dependent on the nature of the working memory modality.

A narrative journey of teacher reflexivity and authenticity in technological environments /

This qualitative narrative inquiry was driven by my desire to further explore my personal discovery that my utilization of educational technologies in teaching and learning environments seemed to heighten a sense of creativity, which in turn increased reflective practice and authenticity in my teaching. A narrative inquiry approach was used as it offered the opportunity to uncover the deeper meanings of authenticity and reflection as participants' personal experiences were coconstructed and reconstructed in relationship with me and in relationship to a social milieu. To gain further insight into this potential phenomenon, I engaged in 2 conversational interviews with 2 other teachers from an Ontario College in a large urban centre who have utilized educational technologies in their teaching and learning communities and I maintained a research journal, constructed during the interview process, to record my own emerging narrative accounts, reflections, insights and further questions. The field texts consisted of transcriptions of the interviews and my reflective journal. Research texts were developed as field texts were listened to multiple times and texts were examined for meanings and themes. The educational technologies that both women focused on in the interview were digital video of children as they play, learn and develop and the use of an audible teacher voice in online courses. The invitation given to students to explore and discover meaning in videos of children as they watched them with the teacher seemed to be a catalyst for authenticity and a sense of synergy in the classroom. The power of the audible teacher voice came through as an essential component in online learning environments to offer students a sense of humanness and connection with the teacher. Relationships in both online and face to face classrooms emerged as a necessary and central component to all teaching and learning communities. The theme of paradox also emerged as participants recognized that educational technologies can be used in ways that enhance creativity, authenticity, reflection and relationships or in ways that hinder these qualities in the teaching and learning community. Knowledge of the common experiences of college educators who utilize educational technologies, specifically digital video of children to educate early childhood educators, might give meaning and insight to inform the practice of other teachers who seek authentic, reflexive practice in the classroom and in on line environments.

An exploration of intergenerational exchanges between grandparents and their older grandcildren

Changes within the family unit have resulted in changes in interactions between grandparents and older grandchildren. Existing research indicates that these relationships can result in positive outcomes. A relevant task for researchers is to continue to explore th~se intergenerational relationships. This qualitative phenomenological study explores the question: What functional patterns exist when grandparents interact with older grandchildren? Six grandparent-older grandchild pairs agreed to be involved. Kennedy's (1992) formulation of grandparent-older grandchild activity clusters was reviewed and revised. Activities were clustered related to socialization, companionship, support, entertainment, and education. Findings unique to this study indicate that shared activities were mutually chosen with consideration of activity tolerance, and were consistently evaluated as enjoyable. Partners were chosen because of a comfortable relationship established through frequent past and present interactions, and not because of family lineage preferences. Both grandparents and older grandchildren stated a desire to have a generation peer share activities with them. Exploration of dimension concepts for the "McMaster Model of Family Functioning" indicated that these relationships have potential to contribute to healthy family functioning. The implications for practice, theory development and further research are suggested.

Sex chromosome translocation and speciation : a Drosophila genetic model

Although exceptions may be readily identified, two generalizations concerning genetic differences among species may be drawn from the available allozyme and chromosome data. First, structural gene differences among species vary widely. In many cases, species pairs do not differ more than intraspecific populations. This suggests that either very few or no gene substitutions are required to produce barriers to reproduction (Avise 1976). Second, chromosome form and/or number differs among even closely related species (White 1963; 1978; Fredga 1977; Wright 1970). Many of the observed chromosomal differences involve translocational rearrangements; these produce severe fitness depression in heterozygotes and were, thus, long considered unlikely candidates for the fixation required of genetic changes leading to speciation (Wright 1977). Nonetheless, the fact that species differences are frequently translocational argues convincingly for their fixation despite prejudices to the contrary. Haldane's rule states that in the F of interspecific crosses, the heterogametic sex is absent or sterile in the preponderance of cases (Haldane 1932). This rule definitely applies in the genus Dr°sophila (Ehrman 1962). Sex chromosome translocations do not impose a fitness depression as severe as that imposed by autosomal translocations, and X-Y translocations may account for Haldane's rule (Haldane 1932). Consequently a study of the fit ness parameters of an X·yL and a yS chromosome in Drosophila melanogaster populations was initiated by Tracey (1972). Preliminary results suggested that x.yL//YSmales enjoyed a mating advantage with X·yL//X·yL females, that this advantage was frequency dependent, that the translocation produced sexual isolation and that interactions between the yL, yS and a yellow marker contributed to the observed isolation (Tracey and Espinet 1976; Espinet and Tracey 1976). Encouraged by the results of these prelimimary studies, further experiments were performed to clarify the genetic nature of the observed sexual isolation, S the reality of the y frequency dependent fitness .and the behavioural changes, if any, produced by the translocation. The results of this work are reported herein. Although the marker genes used in earlier studies, sparkling poliert an d yellow have both been found to affect activity,but only yellow effects asymmetric sexual isolation. In addition yellow effects isolation through an interaction with the T(X-y) chromosomes, yS also effects isolation, and translocational strains are isolated from those of normal karyotype in the absence of marker gene differences. When yS chromosomes are in competition with y chromosomes on an X.yL background, yS males are at a distinct advantage only when their frequency is less than 97%. The sex chromosome translocation alters the normal courtship pattern by the incorporation of circling between vibration and licking in the male repertoire. Finally a model of speciation base on the fixation of this sex chromosome translocation in a geographically isolated gene pool is proposed.

Investigations into the determination of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) by capillary gas chromatography

Factors involved in the determination of PAHs (16 priority PAHs as an example) and PCBs (10 PCB congeners, representing 10 isomeric groups) by capillary gas chromatography coupled with mass spectrometry (GC/MS, for PAHs) and electron capture detection (GC/ECD , for PCBs) were studied, with emphasis on the effect of solvent. Having various volatilities and different polarities, solvent studied included dichloromethane, acetonitrile, hexan e, cyclohexane, isooctane, octane, nonane, dodecane, benzene, toluene, p-xylene, o-xylene, and mesitylene. Temperatures of the capillary column, the injection port, the GC/MS interface, the flow rates of carrier gas and make-up gas, and the injection volume were optimized by one factor at a time method or simplex optimization method. Under the optimized conditions, both peak height and peak area of 16 PAHs, especially the late-eluting PAHs, were significantly enhanced (1 to 500 times) by using relatively higher boiling point solvents such as p-xylene and nonane, compared with commonly used solvents like benzene and isooctane. With the improved sensitivity, detection limits of between 4.4 pg for naphthalene and 30.8 pg for benzo[g,h,i]perylene were obtained when p-xylene was used as an injection solvent. Effect of solvent on peak shape and peak intensity were found to be greatly dependent on temperature parameters, especially the initial temperature of the capillary column. The relationship between initial temperature and shape of peaks from 16 PAHs and 10 PCBs were studied and compared when toluene, p-xylene, isooctane, and nonane were used as injection solvents. If a too low initial temperature was used, fronting or split of peaks was observed. On the other hand, peak tailing occurred at a too high initial column temperature. The optimum initial temperature, at which both peak fronting and tailing were avoided and symmetrical peaks were obtained, depended on both solvents and the stationary phase of the column used. On a methyl silicone column, the alkane solvents provided wider optimum ranges of initial temperature than aromatic solvents did, for achieving well-shaped symmetrical GC peaks. On a 5% diphenyl: 1% vinyl: 94% dimethyl polysiloxane column, when the aromatic solvents were used, the optimum initial temperature ranges for solutes to form symmetrical peaks were improved to a similar degree as those when the alkanes were used as injection solvents. A mechanism, based on the properties of and possible interactions among the analyte, the injection solvent, and the stationary phase of the capillary column, was proposed to explain these observations. The effect of initial temperature on peak height and peak area of the 16 PAHs and the 10 PCBs was also studied. The optimum initial temperature was found to be dependent on the physical properties of the solvent used and the amount of the solvent injected. Generally, from the boiling point of the solvent to 10 0C above its boiling point was an optimum range of initial temperature at which cthe highest peak height and peak area were obtained.

Magnetic and transport properties of (Ba1-xKx)Fe2As2

Single crystals of (Bal - xKx)Fe2As2 were prepared using the Sn flux method. Two heating methods were used to prepare the single crystals: the slow heating and rapid heating methods. It was found that the single crystals grown using the slow heating method were not superconducting due to a significant loss of potassium. When the rapid heating method was used, the single crystals were observed to be superconducting with the desired potassium concentration. The energy dispersive X-ray spectroscopy analysis indicated the presence of multiple phases in the single crystals. Using single crystal X-ray diffraction, the crystal structure of the single crystals was found to be 14/mmm tetragonal at room temperature. The magnetic measurements on the single crystals indicated the presence of multiple phases and magnetic impurities.

An exploratory study for the discovery of non-invasive hepatocellular carcinoma biomarkers among high-risk hepatitis C virus infected patients

Hepatocellular Carcinoma (HCC) is a major healthcare problem, representing the third most common cause of cancer-related mortality worldwide. Chronic infections with Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) are the major risk factors for the development of HCC. The incidence of HBV -associated HCC is in decline as a result of an effective HBV vaccine; however, since an equally effective HCV vaccine has not yet been developed, there are 130 million HCV infected patients worldwide who are at a high-risk for developing HCC. Because reliable parameters and/or tools for the early detection of HCC among high-risk individuals are severely lacking, HCC patients are always diagnosed at a late stage where surgical solutions or effective treatment are not possible. Using urine as a non-invasive sample source, two different approaches (proteomic-based and genomic-based approaches) were pursued with the common goal of discovering potential biomarker candidates for the early detection of HCC among high-risk chronic HCV infected patients. Urine was collected from 106 HCV infected Egyptian patients, 32 of whom had already developed HCC and 74 patients who were diagnosed as HCC-free at the time of initial sample collection. In addition to these patients, urine samples were also collected from 12 healthy control individuals. Total urinary proteins, Trans-renal nucleic acid (Tr-NA) and microRNA (miRNA) were isolated from urine using novel methodologies and silicon carbide-loaded spin columns. In the first, "proteomic-based", approach, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to identify potential candidates from pooled urine samples. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR (qRT-PCR). This approach revealed that significant over-expression of three proteins: DJ-1, Chromatin Assembly Factor-1 (CAF-1) and 11 Moemen Abdalla HCC Biomarkers Heat Shock Protein 60 (HSP60), were characteristic events among HCC-post HCV infected patients. As a single-based HCC biomarker, CAF-1 over-expression identified HCC among HCV infected patients with a specificity of 90%, sensitivity of 66% and with an overall diagnostic accuracy of 78%. Moreover, the CAF-lIHSP60 tandem identified HCC among HCV infected patients with a specificity of 92%, sensitivity of 61 % and with an overall diagnostic accuracy of 77%. In the second genomic-based approach, two different approaches were processed. The first approach was the miRNA-based approach. The expression levels of miRNAs isolated from urine were studied using the Illumina MicroRNA Expression Profiling Assay. This was followed by qRT-PCR-based validation of deregulated expression of identified miRNA candidates among all the patients. This approach shed the light on the deregulated expression of a number of miRNAs, which may have a role in either the development of HCC among HCV infected patients (i.e. miR-640, miR-765, miR-200a, miR-521 and miR-520) or may allow for a better understanding of the viral-host interaction (miR-152, miR-486, miR-219, miR452, miR-425, miR-154 and miR-31). Moreover, the deregulated expression of both miR-618 and miR-650 appeared to be a common event among HCC-post HCV infected patients. The results of the search for putative targets of these two miRNA suggested that miR-618 may be a potent oncogene, as it targets the tumor-suppressor gene Low density lipoprotein-related protein 12 (LPR12), while miR-650 may be a potent tumor-suppressor gene, as it is supposed to downregulate the TNF receptor-associated factor-4 (TRAF4) oncogene. The specificity of miR-618 and miR-650 deregulated expression patterns for the early detection of HCC among HCV infected patients was 68% and 58%, respectively, whereas the sensitivity was 64% and 72%, respectively. When the deregulated expression of both miRNAs was combined as a tandem biomarker, the specificity and the sensitivity were 75% and 58% respectively. 111 Moemen Abdalla HCC Biomarkers In the second, "Trans-renal nucleic acid-based", approach, the urinary apoptotic nucleic acid (uaNA) levels of 70ng/mL or more were found to be a good predictor of HCC among chronic HCV infected patients. The specificity and the sensitivity of this diagnostic approach were 76% and 86%, respectively, with an overall diagnostic value of 81 %. The uaNA levels positively correlated to HCC disease progression as monitored by epigenetic changes of a panel of eight tumor-suppressor genes (TSGs) using methylation-sensitive PCR. Moreover, the pairing of high uaNA levels (:::: 70 ng/mL) and CAF-1 over-expreSSIOn produced a highly specific (l 00%) multiple-based HCC biomarker with an acceptable sensitivity of 64%, and with a diagnostic accuracy of 82%. In comparison to the previous pairing, the uaNA levels (:::: 70 ng/mL) in tandem with HSP60 over-expression was less specific (89%) but highly sensitive (72%), resulting in a diagnostic accuracy of 64%. The specificities of miR-650 deregulated expression in combination with either high uaNA content or HSP 60 over-expression were 82% and 79%, respectively, whereas, the sensitivities of these combinations were 64% and 58%, respectively. The potential biomarkers identified in this study compare favorably with the diagnostic accuracy of the a-fetoprotein levels test, which has a specificity of 75%, sensitivity of 68% and an overall diagnostic accuracy of 70%. Here we present an intriguing study which shows the significance of using urine as a noninvasive sample source for the identification of promising HCC biomarkers. We have also introduced new techniques for the isolation of different urinary macromolecules, especially miRNA, from urine. Furthermore, we strongly recommend the potential biomarkers indentified in this study as focal points of any future research on HCC diagnosis. A larger testing pool will determine if their use is practical for mass population screening. This explorative study identified potential targets that merit further investigation for the development of diagnostically accurate biomarkers isolated from 1-2 mL urine samples that were acquired in a non-invasive manner.

TA tales : [re]storying the teaching and learning experiences of university teaching assistants

This inquiry examines reported critical incidents that shaped the lived experience of 5 university TAs as they negotiated multiple roles and relationships within the teaching and learning context. Questions and ensuing conversations explore the ways in which these critical incidents in teaching contributed to the TAs' understanding of themselves as teachers, of teaching and learning tensions in higher education, and of the institutional contexts in which they work. The inquiry also explores the ways in which narrative, particularly creative fiction, can represent the stories TAs tell of their experiences.

A Study of Ordered Gene Problems Featuring DNA Error Correction and DNA Fragment Assembly with a Variety of Heuristics, Genetic Algorithm Variations, and Dynamic Representations

Ordered gene problems are a very common classification of optimization problems. Because of their popularity countless algorithms have been developed in an attempt to find high quality solutions to the problems. It is also common to see many different types of problems reduced to ordered gene style problems as there are many popular heuristics and metaheuristics for them due to their popularity. Multiple ordered gene problems are studied, namely, the travelling salesman problem, bin packing problem, and graph colouring problem. In addition, two bioinformatics problems not traditionally seen as ordered gene problems are studied: DNA error correction and DNA fragment assembly. These problems are studied with multiple variations and combinations of heuristics and metaheuristics with two distinct types or representations. The majority of the algorithms are built around the Recentering- Restarting Genetic Algorithm. The algorithm variations were successful on all problems studied, and particularly for the two bioinformatics problems. For DNA Error Correction multiple cases were found with 100% of the codes being corrected. The algorithm variations were also able to beat all other state-of-the-art DNA Fragment Assemblers on 13 out of 16 benchmark problem instances.

The Influence of Burnout Symptoms on the Relationship between Work-Life Balance and Self-Rated Health

The effects of stress at work are estimated to cost Canadian employers more than 20 billion dollars annually through absenteeism, sick leave and decreased productivity. Over the past two decades, Canadians have reported higher stress levels, increased work hours and more work performed outside of normal business hours. This work-life imbalance has far-reaching repercussions–affecting an employee’s performance as well as their health. Chronic exposure to these high levels of stress can also lead to burnout. The primary purpose of this study was to determine the magnitude in which burnout symptoms influence the relationship between work-life balance and self-rated health. The secondary purpose of this study was to determine if gender and age interactions exist in the relationship between burnout, work-life balance, and self-rated health. This cross-sectional study involved secondary analysis of 220 managers, workers and human service professionals who completed an Occupational Health Clinics for Ontario Workers’ Mental Injury Toolkit (MIT) survey for the launch of the MIT. The MIT survey is a modified form of the short version of the Copenhagen Psychosocial Questionnaire and includes expanded questioning around burnout, stress, sleep troubles, cognitive, and somatic symptoms. There were no significant differences in self-rated health based on a respondent’s gender or age, indicating that no interaction of gender and age would be required. Respondents with low self-rated health reported significantly higher burnout and work-life imbalance compared to those with high self-rated health. The regression analysis demonstrated that the magnitude in which burnout mediates the relationship between work-life balance and self-rated health was 96%. These findings support previous studies that associate high levels of work-life imbalance or burnout with poor self-rated health or health outcomes. In this study, the shared variance between work-life balance and burnout also supports recent efforts to redefine the context and causes of burnout to include non-work factors. Based on our findings, the potential exists for the development of workplace health promotion strategies that address maintaining a balance between work and home as they may improve employee health and reduce burnout.