p38 MAPK and the C2C12 cell cycle : in vitro and in silico investigations.

Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.The mammalian cell cycle and its points-of-entry are well characterized pathways. These points-of-entry are normally regulated via mitogens and include, amongst others, the ERK, JNK and p38 mitogen-activated protein kinase (MAPK) pathways. However, while the restriction point(R-point), the temporal switch-point at which a cell becomes irrevocably committed to division irrespective of mitogenic stimulus, is known among other cell types, its position within the murine myoblast line C2C12 is currently unknown. Similarly, while MAPK pathways, such as JNK and ERK, have been modeled computationally, no model yet exists of p38 MAPK as stimulated by mitogens. The aims of this dissertation, then, were to determine the R-point within the C2C12 cell cycle and construct a computational mitogen-stimulated p38 MAPK model. It was found that a synchronous C2C12 population, when stimulated to divide, took 7 to 9 hours to reach S-phase from G0, consistent with data from the literature. The R-point was determined to lie between 6 and 7 hours post G1-re-entry stimulation,which was consistent with studies in other cell types. Core modeling of the p38 MAPK pathway revealed that ultrasensitivitywas inherent within the pathway structure. Further, a branching/re-converging structure within the pathway imparted greater responsiveness to signal upon the pathway. A realistic p38 MAPK model demonstrated good responsiveness to signal, its output matched that of several other MAPK models, and it was capable of replicating previous in vitro data. This model can be used as a tool for further investigation of the mammalian cell cycle by linking it to other cell cycle models. The predictions by an expanded model may be better suited for understanding the effects of mitogen stimulus on the cell cycle in situ

Hypersonic Vehicle Flight Dynamics with Coupled Aerodynamic and Reduced-Order Propulsive Models

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83644/1/AIAA-2010-7930-291.pd

Anatomy and growth of a Holocene clinothem in the Gulf of Papua

High-resolution seismic profiles and sedimentological data from grab samples and long cores provide an unprecedented picture of the structure, sedimentology, and late Quaternary development of two Gulf of Papua ( GoP) clinothems, one probably Stage 3 and 4 in age and one Holocene in age. The older was partially eroded during Stage 2 and partially covered by the younger clinothem during Stage 1. The younger clinothem consists of three stratigraphic units separated by two surfaces of erosion, bypass, or correlative surfaces of lap. The surfaces were formed by changes in accommodation and sediment supply. The underlying physiography of the older clinothem also appears to play an important role in governing the shape of the younger clinothem. In the northern gulf, oblique clinoforms of the younger clinothem suggest that the rate of sediment supply from the northern rivers outstripped the formation of new accommodation, whereas in the south, sigmoidal clinoforms indicate that accommodation increased faster than sediment supply. The origin of the new accommodation remains uncertain because of limited age constraints. On the basis of sediment thickness, stratal geometry, and acoustic character, off-shelf transport appears to be the dominant sediment transport direction, with preferential accumulation on the promontories and bypass in the valleys. Presently, observed and computed modern flows and complex gyres in shallow water coupled with wave- and current-supported gravity flows or river floods can explain the form, internal clinoform shapes, and mineralogy of the younger Gulf of Papua clinothem

Creating a Legal Framework for Copyright Management of Open Access within the Australian Academic and Research Sector

There is an increasing recognition, in Australia and internationally, that access to knowledge is a key driver of social, cultural and economic development. The argument for greater access to, and reuse of, research outputs is reinforced by the fact that much research in Australia is funded by public money and, consequently, that there is a public benefit to be served by allowing citizens to access the outputs they have funded.2 This recognition poses both legal and policy challenges, in terms of existing legal frameworks such as copyright law and traditional business models. With the rise of networked digital technologies our knowledge landscape and innovation system is becoming more and more reliant on best practice copyright management strategies and there is a need to accommodate both the demands for open sharing of knowledge and traditional commercialisation models. As a result, new business models that support and promote open innovation are rapidly emerging. This chapter analyses the copyright law framework needed to ensure open access to outputs of the Australian academic and research sector such as journal articles and theses. It overviews the new knowledge landscape, the principles of copyright law, the concept of open access to knowledge, the recently developed open content models of copyright licensing and the challenges faced in providing greater access to knowledge and research outputs

Measuring ‘self’: preliminary validation of a short form of the self experiences questionnaire in people with chronic pain

Background: People with chronic pain often struggle with their sense of self and this can adversely impact their functioning and wellbeing. Acceptance and Commitment Therapy particularly includes a process related to this struggle with self. A measure for this process, the Self Experiences Questionnaire, was previously developed in people with chronic pain. Purpose: The aim of the current study was to validate a shorter version of the Self Experiences Questionnaire in people with chronic pain to reduce respondent burden and facilitate further research. Methods: Data from 477 participants attending an interdisciplinary pain management programme were included. Participants completed measures of treatment processes (self-as-context, pain acceptance, cognitive fusion, and committed action) and outcomes (pain, pain interference, work and social adjustment, and depression) at baseline and post-treatment. Confirmatory factor analysis was used for item reduction. Correlations between scores from the shorter Self Experiences Questionnaire and other process and outcome variables were calculated to examine validity. Change scores of the shorter Self Experiences Questionnaire and their correlations with changes in outcome variables were examined for responsiveness. Results: An eight-item SEQ (SEQ-8) scale including two factors, namely Self-as-Distinction and Self-as-Observer, emerged, demonstrating good reliability (Cronbach’s α=.87-.90) and validity (|r|=.14-.52). Scores from SEQ-8 significantly improved after the treatment (d=.15-21), and these improvements correlated with improvements in most outcomes. Conclusions: The SEQ-8 appears to be a reliable and valid measure of self. This shorter format may facilitate intensive longitudinal investigation into sense of self and functioning and wellbeing

Specimen collection for the diagnosis of pediatric pneumonia.

Diagnosing the etiologic agent of pneumonia has an essential role in ensuring the most appropriate and effective therapy for individual patients and is critical to guiding the development of treatment and prevention strategies. However, establishing the etiology of pneumonia remains challenging because of the relative inaccessibility of the infected tissue and the difficulty in obtaining samples without contamination by upper respiratory tract secretions. Here, we review the published and unpublished literature on various specimens available for the diagnosis of pediatric pneumonia. We discuss the advantages and limitations of each specimen, and discuss the rationale for the specimens to be collected for the Pneumonia Etiology Research for Child Health study

Identification and Selection of Cases and Controls in the Pneumonia Etiology Research for Child Health Project

Methods for the identification and selection of patients (cases) with severe or very severe pneumonia and controls for the Pneumonia Etiology Research for Child Health (PERCH) project were needed. Issues considered include eligibility criteria and sampling strategies, whether to enroll hospital or community controls, whether to exclude controls with upper respiratory tract infection (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH ultimately decided to enroll community controls and an additional human immunodeficiency virus (HIV)–infected control group at high HIV-prevalence sites matched on age and enrollment date of cases; controls with symptoms of URTI or nonsevere pneumonia will not be excluded. Systematic sampling of cases (when necessary) and random sampling of controls will be implemented. For each issue, we present the options that were considered, the advantages and disadvantages of each, the rationale for the methods selected for PERCH, and remaining implications and limitations

Exploring a collaborative approach to the involvement of patients, carers and the public in the initial education and training of healthcare professionals: A qualitative study of patient experiences

Objective This study aimed to explore patients' experiences of their involvement in the design and delivery of interprofessional education interventions focussing on mental ill-health for students studying in undergraduate healthcare and healthcare-related programmes. Design A qualitative methodology using a Grounded Theory approach was used to undertake an iterative series of focus groups with members of a university's Patient, Carer and Public Involvement (PCPI) Group who have a history of mental ill-health and were involved in the development and delivery of educational interventions for students on undergraduate healthcare and healthcare-related programmes. Their experiences of being involved in teaching and learning activities, collaboration with academic staff and integration into the academic faculty were explored. Constant comparative analysis facilitated the identification and prioritisation of salient themes. Results Five salient inter-related themes emerged from the data: (1) reduced stigma and normalisation of experience of illness; (2) enhanced self-worth; (3) improved well-being; (4) community and connection; and (5) enduring benefits. Conclusions A supportive university community and a designated academic PCPI co-ordinator facilitate a supportive environment for patients and carers to develop as educators, contribute to the training of future healthcare professionals and improve their own personal well-being. Appropriately resourced and well-supported initiatives to integrate patients, carers and the public into the functions of an academic faculty can result in tangible benefits to individuals and facilitate meaningful and enduring connections between the university and the wider community within which it is situated. Patient and Public Involvement Patients have been involved in the design of the teaching and learning initiatives that this study was primarily focused on. Patients were given autonomy in determining how their experiences should be incorporated into teaching and learning experiences