A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation of the inflammatory response in the lung

Introduction: Secretory leucocyte protease inhibitor and elafin are members of the whey acidic protein (WAP), or WAP four disulfide-core (WFDC), family of proteins and have multiple contributions to innate defence including inhibition of neutrophil serine proteases and inhibition of the inflammatory response to lipopolysaccharide (LPS). This study aimed to explore potential activities of WFDC12, a previously uncharacterised WFDC protein expressed in the lung. Methods: Recombinant expression and purification of WFDC12 were optimised in Escherichia coli. Antiprotease, antibacterial and immunomodulatory activities of recombinant WFDC12 were evaluated and levels of endogenous WFDC12 protein were characterised by immunostaining and ELISA. Results: Recombinant WFDC12 inhibited cathepsin G, but not elastase or proteinase-3 activity. Monocytic cells pretreated with recombinant WFDC12 before LPS stimulation produced significantly lower levels of the pro-inflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared with cells stimulated with LPS alone. Recombinant WFDC12 became conjugated to fibronectin in a transglutaminase-mediated reaction and retained antiprotease activity. In vivo WFDC12 expression was confirmed by immunostaining of human lung tissue sections. WFDC12 levels in human bronchoalveolar lavage fluid from healthy and lung-injured patients were quantitatively compared, showing WFDC12 to be elevated in both patients with acute respiratory distress syndrome and healthy subjects treated with LPS, relative to healthy controls. Conclusions: Together, these results suggest a role for this lesser known WFDC protein in the regulation of lung inflammation.

Recent Developments in the Analysis of the Black Mat Layer and Cosmic Impact at 12.8ka

Recent analyses of sediment samples from "black mat" sites in South America and Europe support previous interpretations of an ET impact event that reversed the Late Glacial demise of LGM ice during the Bølling Allerød warming, resulting in a resurgence of ice termed the Younger Dryas (YD) cooling episode. The breakup or impact of a cosmic vehicle at the YD boundary coincides with the onset of a 1-kyr long interval of glacial resurgence, one of the most studied events of the Late Pleistocene. New analytical databases reveal a corpus of data indicating that the cosmic impact was a real event, most possibly a cosmic airburst from Earth's encounter with the Taurid Complex comet or unknown asteroid, an event that led to cosmic fragments exploding interhemispherically over widely dispersed areas, including the northern Andes of Venezuela and the Alps on the Italian/French frontier. While the databases in the two areas differ somewhat, the overall interpretation is that microtextural evidence in weathering rinds and in sands of associated paleosols and glaciofluvial deposits carry undeniable attributes of melted glassy carbon and Fe spherules, planar deformation features, shock-melted and contorted quartz, occasional transition and platinum metals, and brecciated and impacted minerals of diverse lithologies. In concert with other black mat localities in the Western USA, the Netherlands, coastal France, Syria, Central Asia, Peru, Argentina and Mexico, it appears that a widespread cosmic impact by an asteroid or comet is responsible for deposition of the black mat at the onset of the YD glacial event. Whether or not the impact caused a 1-kyr interval of glacial climate depends upon whether or not the Earth had multiple centuries-long episodic encounters with the Taurid Complex or asteroid remnants; impact-related changes in microclimates sustained climatic forcing sufficient to maintain positive mass balances in the reformed ice; and/or inertia in the Atlantic thermohaline circulation system persisted for 1kyr. 

The role of the cathelicidin LL-37 in periodontal disease.

Abstract Background Fibroblasts respond to bacterial stimulation by producing an array of inflammatory cytokines and chemokines. As such fibroblasts play a significant role as regulators of the host response in periodontal disease. LL-37, an antimicrobial peptide, found in saliva and GCF, inhibits LPS-induced cytokine signalling in macrophages, suggesting a role in host defence in periodontal disease. This study investigated the interaction between LL-37 and gingival fibroblasts – both its direct regulation of fibroblast activity and also its effect on fibroblast response to LPS activation. Methods Human gingival fibroblasts (HGFs) were incubated for 24 hours in the presence of either P. gingivalis LPS (10µg/ml) or E. coli LPS (0.01µg/ml) along with LL-37 (0-50µg/ml). IL-6 and IL-8 production by HGFs in the conditioned medium was determined by ELISA. DNA microarray analysis was performed on cell populations incubated for 6 hr in the presence or absence of the peptide. Results At low concentrations (≤ 5 µg/ml) LL-37 significantly inhibited LPS-induced cytokine production by HGFs. At higher concentrations LL37 induced IL-8 production independent of LPS. Microarray analysis revealed that LL-37 upregulated a significant number of cytokines and chemokines by > 5 fold. The stimulatory effect on IL-8 mRNA expression was confirmed by Q-PCR. Conclusion LL-37 appears to have pleiotrophic effects in innate immunity. Its ability, at low concentrations, to reduce bacterial LPS-induced cytokine production in gingival fibroblasts suggests a potential therapeutic role in the management of periodontal disease.

Networked learning ten years on: the rise of the virtual graduate school

The aim of this paper is to reflect on how conceptions of networked learning have changed, particularly in relation to educational practices and uses of technology, that can nurture new ideas of networked learning to sustain multiple and diverse communities of practice in institutional settings. Our work is framed using two theoretical frameworks: Giddens's (1984) structuration theory and Callon & Latour's (1981) Actor Network Theory as critiqued by Fox (2005) in relation to networked learning. We use these frameworks to analyse and critique ideas of networked learning embodied in both cases. We investigate three questions: (a) the role of individual agency in the development of networked learning; (b) the impact of technological developments on approaches to supporting students within institutional infrastructures; and (c) designing networked learning to incorporate Web 2.0 practices that sustain multiple communities and foster engagement with knowledge in new ways. We use an interpretivist approach by drawing on experiential knowledge of the Masters programme in Networked Collaborative Learning and the decision making process of designing the virtual graduate schools. At this early stage, we have limited empirical data related to the student experience of networked learning in current and earlier projects. Our findings indicate that the use of two different theoretical frameworks provided an essential tool in illuminating, situating and informing the process of designing networked learning that involves supporting multiple and diverse communities of practice in institutional settings. These theoretical frameworks have also helped us to analyze our existing projects as case studies and to problematize and begin to understand the challenges we face in facilitating the participation of research students in networked learning communities of practice and the barriers to that participation. We have also found that this process of theorizing has given us a way of reconceptualizing communities of practice within research settings that have the potential to lead to new ideas of networked learning.

Modelling adhesive joints with cohesive zone models: effect of the cohesive law shape of the adhesive layer

Adhesively-bonded joints are extensively used in several fields of engineering. Cohesive Zone Models (CZM) have been used for the strength prediction of adhesive joints, as an add-in to Finite Element (FE) analyses that allows simulation of damage growth, by consideration of energetic principles. A useful feature of CZM is that different shapes can be developed for the cohesive laws, depending on the nature of the material or interface to be simulated, allowing an accurate strength prediction. This work studies the influence of the CZM shape (triangular, exponential or trapezoidal) used to model a thin adhesive layer in single-lap adhesive joints, for an estimation of its influence on the strength prediction under different material conditions. By performing this study, guidelines are provided on the possibility to use a CZM shape that may not be the most suited for a particular adhesive, but that may be more straightforward to use/implement and have less convergence problems (e.g. triangular shaped CZM), thus attaining the solution faster. The overall results showed that joints bonded with ductile adhesives are highly influenced by the CZM shape, and that the trapezoidal shape fits best the experimental data. Moreover, the smaller is the overlap length (LO), the greater is the influence of the CZM shape. On the other hand, the influence of the CZM shape can be neglected when using brittle adhesives, without compromising too much the accuracy of the strength predictions.

Basal and antigen-induced exposure of the proline-rich sequence in CD3ε.

The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ("open-CD3"), although most TCR-CD3 complexes were inaccessible to Nck ("closed-CD3"). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.

From protest to powerlessness : a Marxist analysis of the Ontario NDP /

Using Marxist state theory as an analytical framework, this thesis explains the problems faced by the Ontario New Democratic Party government (1990-1995) in implementing a social democratic agenda. Not only was the government constrained in its ability to implement progressive policy, but it was also pushed to implement a Social Contract (involving legislated wage cuts to public sector employees) that alienated the party's base of support, making it more difficult for the party to organize in the future. Although this study relies predominantly on a reinterpretation of existing research on the topic, some primary research is used in the analysis, including interviews with members of the labour movement and former MPPs and analysis of the news media's treatment of the party/ government. Historical and class analytical perspectives are used to explain the evolution of the ONDP's structure and policies, as well as to assess the relative strength of the working class and its ability to support a social democratic political agenda. It was found that the ONDP' s unwillingness to develop a long term plan for social democracy, and its inability to act as a mass party or to build a strong working class movement, made it more difficult for the party to succeed when it formed the government. Moreover, the class nature of the capitalist state, along with pressure exerted by a well mobilized capitalist class, worked to limit the government' s options.

Public service reform and the role of the Auditor General /

The objective of this thesis is to study the involvement of the Auditor General in the proposal, implementation and review of major public service reform initiatives during a period spanning nearly forty years, from the early 1960s to 2001 . This period began with the Glassco Commission and concludes at the end of the term in office of Auditor General Denis Desautels in 2001. It has been demonstrated throughout this work that the role of the OAG has varied, from proponent to critic, from instigator to reviewer. In the past forty years the OAG's mandate has changed to meet the requirements of critical analysis of government operations and this has been aptly demonstrated in the office's relationship to the issue of public service reform. It has been argued that many of the problems facing the public service are cultural in nature. Reform initiatives have taken on a number of various forms with each addressing a different set of priorities. However, there has been a great deal of consistency in the cultural values that these initiatives articulate. Throughout this thesis attention has been paid to values. Values define a culture and cultural change is required within the Canadian federal public service. How and when this cultural change will occur is but one question to be answered. During the period under consideration in this thesis the government undertook several significant public service reform initiatives. Those examined in this thesis include: The Royal Commission on Government Organization, The Special Committee on the Review of Personnel Management and the Merit Principle, The Royal Commission on Financial Management and Accountability, Increased Ministerial Authority and Accountability, Public Service 2000, Program Review and finally La Releve. The involvement, or interest, of the Auditor General's Office on the subject of public service reform is generally articulated through the means of its annual reports to Parliament although there have been supplementary undertakings on this issue. Such material relevant to this study include: Towards Better Governance: Public Service Reform in New Zealand (1984-94) and its Relevance to Canada and Reform in the Australian Public Service. Annual reports to Parliament include: "Values, Service and Performance," (1990), "Canada's Public Service Reform and Lessons Learned from Selected Jurisdictions," (1993), "Maintaining a Competent and Efficient Public Service," (1997), and "Expenditure and Work Force Reduction in Selected Departments,"

The effect of moisture on decomposition processes in the disturbed peatlands of the Wainfleet bog /

The purpose of this study was to determine the effect of increased soil moisture levels on the decomposition processes in a peat-extracted bog. Field experiments, in which soil moisture levels were manipulated, were conducted using 320 microcosms in the Wainfleet Bog from May 2002 to November 2004. Decomposition was measured using litter bags and monitoring the abundance of macro invertebrate decomposers known as Collembola. Litter bags containing wooden toothpicks (n=2240), filter paper (n=480) and Betula pendula leaves (n=40) were buried in the soil and removed at regular time intervals up to one year. The results of the litter bag studies demonstrated a significant reduction of the decomposition of toothpicks (p<0.001), filter paper (p<0.001), and Betula pendula leaves (pof natural conditions. These conditions significantly reduced the mean mass loss of toothpicks by 30 %, filter paper by 20 % and Betula pendula leaves by 18 % over one year when compared to the control. The abundance of Collembola was monitored using a non-destructive method in the microcosms. By contrast the effect of increased moisture levels on the abundance of Collembola was more variable and difficult to interpret. The conclusions of this study indicate that the Wainfleet Bog is a highly disturbed peatland and that the greatest reductions in decomposition can be obtained by restoring the soil moisture levels near those of undisturbed conditions.

Information processing in sleep-onset insomnia : a test of the neurocognitive model /

The present thesis study is a systematic investigation of information processing at sleep onset, using auditory event-related potentials (ERPs) as a test of the neurocognitive model of insomnia. Insomnia is an extremely prevalent disorder in society resulting in problems with daytime functioning (e.g., memory, concentration, job performance, mood, job and driving safety). Various models have been put forth in an effort to better understand the etiology and pathophysiology of this disorder. One of the newer models, the neurocognitive model of insomnia, suggests that chronic insomnia occurs through conditioned central nervous system arousal. This arousal is reflected through increased information processing which may interfere with sleep initiation or maintenance. The present thesis employed event-related potentials as a direct method to test information processing during the sleep-onset period. Thirteen poor sleepers with sleep-onset insomnia and 1 2 good sleepers participated in the present study. All poor sleepers met the diagnostic criteria for psychophysiological insomnia and had a complaint of problems with sleep initiation. All good sleepers reported no trouble sleeping and no excessive daytime sleepiness. Good and poor sleepers spent two nights at the Brock University Sleep Research Laboratory. The first night was used to screen for sleep disorders; the second night was used to investigate information processing during the sleep-onset period. Both groups underwent a repeated sleep-onsets task during which an auditory oddball paradigm was delivered. Participants signalled detection of a higher pitch target tone with a button press as they fell asleep. In addition, waking alert ERPs were recorded 1 hour before and after sleep on both Nights 1 and 2.As predicted by the neurocognitive model of insomnia, increased CNS activity was found in the poor sleepers; this was reflected by their smaller amplitude P2 component seen during wake of the sleep-onset period. Unlike the P2 component, the Nl, N350, and P300 did not vary between the groups. The smaller P2 seen in our poor sleepers indicates that they have a deficit in the sleep initiation processes. Specifically, poor sleepers do not disengage their attention from the outside environment to the same extent as good sleepers during the sleep-onset period. The lack of findings for the N350 suggest that this sleep component may be intact in those with insomnia and that it is the waking components (i.e., Nl, P2) that may be leading to the deficit in sleep initiation. Further, it may be that the mechanism responsible for the disruption of sleep initiation in the poor sleepers is most reflected by the P2 component. Future research investigating ERPs in insomnia should focus on the identification of the components most sensitive to sleep disruption. As well, methods should be developed in order to more clearly identify the various types of insomnia populations in research contexts (e.g., psychophysiological vs. sleep-state misperception) and the various individual (personality characteristics, motivation) and environmental factors (arousal-related variables) that influence particular ERP components. Insomnia has serious consequences for health, safety, and daytime functioning, thus research efforts should continue in order to help alleviate this highly prevalent condition.

Environmental assessment of Lake Gibson sediments, water quality, and soils of the Niagara Region

In light of the fact that literature on toxicity of heavy metals in non-acidified freshwater systems is sparse, this project was initiated to conduct an environmental assessment of Lake Gibson. Chemistry of soils from adjacent areas and vineyards in the region provide a comparative background database. Water quality determinations were used to identify and highlight areas of environmental concern within the Lake Gibson watershed. A Shelby Corer was used to obtain 66 sediment cores from Lake Gibson. These were sectioned according to lithology and color to yield 298 samples. A suite of 122 soil samples was collected in the region and vicinity of Lake Gibson. All were tested for metals and some for Total Petroleum Hydrocarbons (TPH). Evaluation of the results leads to the following conclusions: 1. Metal concentrations ofAI, Cd, Cu, Cr, Pb, Ni, Fe and Zn in soils from the Niagara Region are well below background limits set by the Ministry of the Environment and Energy (MOEE) for provincial soils. 2. There is a spatial and depth difference for some of the metals within the various soils. The Cr, Ni and Pb contents of soils vary throughout the region (p5). In addition, Pb contents tend to be highest in surficial soil samples (p5), an observation consistent with deposition by airborne particulates. 3. The Ni contents of sediments from Lake Gibson fall below the LEL (Lower Effect Level) guideline specified by the MOEE for aquatic ecosystems. 4. All other metal contents exceed the LEL, and in some instances they also exceed the SEL (Severe Effect Level) guideline. In this instance acute toxicity testing of 11 the sediments is required to assess impact on the aquatic biota. 5. Specifically, effluents and discharges from outfalls, roadways, railways and industrial activities are all degrading the local ecosystem. 6. Mineral oil and greases are a major environmental concern in the sediments of Lake Gibson. Ofthe 240 samples tested for TPH, 200 samples exceed the MOEE Open Water Disposal Guideline of 1,500 mg/kg. 7. Four areas within Lake Gibson are especially degraded with respect to TPH. One area is just downstream from the Old WeIland Canal divergence point and waterfall. Other areas of concern are located just south of Beaverdams Road and just west ofthe Ontario Hydro control pipes; south ofthe Village ofBeaverdams. The fourth area of environmental concern and TPH impact is located between Highway 406 and Merrittville Highway.

Ethnic conflicts and international politics : an analysis of the communal regional, and global dimensions of the Cyprus problem

The thesis assesses the impact of international factors on relations between Greek and Turkish Cypriots during and after the Cold War. Through an analysis of the Cyprus problem it explores both why external actors intervene in communal conflicts and how they influence relations between ethnic groups in plural societies. The analytical framework employed throughout the study draws on contributions of International Relations theorists and students of ethnic conflict. The thesis argues that, as in the global political system, relations between ethnic groups in unranked communal systems are anarchic; that is, actors within the system do not recognize a sovereign political authority. In bipolar communal systems dominated by two relatively equal groups, the struggle for security and power often leads to appeals for assistance from external actors. The framework notes that neighboring states and Great Powers may heed calls for assistance, or intervene without a prior request, if it is in their interest to do so. The convergence of regional and global interests in communal affairs exacerbates ethnic conflicts and precludes the development of effective political institutions. The impact of external intervention in ethnic conflicts has the potential to alter the basis of communal relations. The Cyprus problem is examined both during and after the Cold War in order to gauge how global and regional actors and the structure of their respective systems have affected relations between ethnic groups in Cyprus. The thesis argues that Cyprus's descent into civil war in 1963 was due in part to the entrenchment of external interests in the Republic's constitution. The study also notes that power politics involving the United States, Soviet Union, Greece and Turkey continued to affect the development of communal relations throughout the 1960s, 70s, and, 80s. External intervention culminated in July and August 1974, after a Greek sponsored coup was answered by Turkey's invasion and partition of Cyprus. The forced expulsion of Greek Cypriots from the island's northern territories led to the establishment of ethnically homogeneous zones, thus altering the context of communal relations dramatically. The study also examines the role of the United Nations in Cyprus, noting that its failure to settle the dispute was due in large part to a lack of cooperation from Turkey, and the United States' and Soviet Union's acceptance of the status quo following the 1974 invasion and partition of the island. The thesis argues that the deterioration of Greek-Turkish relations in the post-Cold War era has made a solution to the dispute unlikely for the time being. Barring any dramatic changes in relations between communal and regional antagonists, relations between Greek and Turkish Cypriots will continue to develop along the lines established in July/August 1974. The thesis concludes by affirming the validity of its core hypotheses through a brief survey of recent works touching on international politics and ethnic conflict. Questions requiring further research are noted as are elements of the study that require further refinement.

Improving the use of the nursing process: the impact of charting methodology developed from King's conceptual framework on the use of the nursing process

The purpose of this study was to assess the effects of changing a nursing documentation system, developed from King's Conceptual Framework, on the use of the nursing process. The null hypothesis was that there would be no significant increase in the reflection of the use of the nursing process on the nursing care plan or nurses' notes, as a result of using a nursing documentation system developed using King's Conceptual Framework (1981). The design involved the development of a questionnaire that was used to review health records pre and post implementation of a documentation system developed based on King's Conceptual Framework and Theory of Goal Attainment (1981). A Record Completeness Score was obtained from some of the questions. The null hypothesis was rejected. The results of the study have implications for nursing administration and the evaluation of nursing practice. If the use of a documentation system developed from a conceptual framework increases the reflection of the nursing process on the patient's health record, nursing will have the means to measure patient outcomes/goal attainment. All health care organizations and levels of government are focusing on methods to monitor and control the health-care dollar. In order for nursing to clearly determine the costs associated with nursing care, measurement of patient outcomes/goal attainment will need to be possible. In order to measure patient outcomes/goals attainment nurses will need to be able to collect data on their practice. It will be critical that nursing have a documentation system in place which facilitates the reflection of the nursing process within a theoretical framework.

Optimization of the valence energy variance of the CuH molecule

We developed the concept of split-'t to deal with the large molecules (in terms of the number of electrons and nuclear charge Z). This naturally leads to partitioning the local energy into components due to each electron shell. The minimization of the variation of the valence shell local energy is used to optimize a simple two parameter CuH wave function. Molecular properties (spectroscopic constants and the dipole moment) are calculated for the optimized and nearly optimized wave functions using the Variational Quantum Monte Carlo method. Our best results are comparable to those from the single and double configuration interaction (SDCI) method.

Student perceptions of the writing process

Based on the critical research paradigm and using a mix of methodologies, this study examined student perceptions of the process approach used to teach writing. A class of 19 ESL students in an academic writing class at a small university paliicipated in the study. As collaborators in the study, they assessed their personality types using the PET Type Check (Crantoll & Knoop, 1995) and tlleir learning styles using Kolb'sLearning Styles Inventory (1976). Interviews, classroom observations, and journals provided a data base for case studies llilQ teacher reflection. Results indicated that students perceived the prewriting step of brainstonning and peer review as most useful. Student perceptions of the tasks and course and implications for theory and practice are examined.