The p38 mitogen-activated protein kinase regulates interleukin-1beta-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cells

Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, the transcription factor, nuclear factor (NF)-kappaB, is recognized to be a critical determinant of the inflammatory response in intestinal epithelial cells (IECs). However, the precise inter-relationship between the activation of p38 MAPK and activation of the transcription factor NF-kappaB in the intestinal epithelial cell (IEC) system, remains unknown. Here we show that interleukin (IL)-1beta activates all three MAPKs in Caco-2 cells. The production of IL-8 and monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation of the NF-kappaB signalling system revealed that the inhibitory effect was independent of the phosphorylation and degradation of IkappaBalpha, the binding partner of NF-kappaB. This effect was also independent of the DNA binding of the p65 Rel A subunit, as well as transactivation, determined by an NF-kappaB luciferase construct, using both SB 203580 and dominant-negative p38 MAPK. Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription-polymerase chain reaction (RT-PCR) revealed that the inhibitory effect of SB 203580 was associated with a reduction in this parameter. Using an IL-8-luciferase promoter construct, an effect of p38 upon its activation by both pharmacological and dominant-negative p38 construct co-transfection was demonstrated. It is concluded that p38 MAPK influences the expression of chemokines in intestinal epithelial cells, through an effect upon the activation of the chemokine promoter, and does not directly involve the activation of the transcription factor NF-kappaB

Securing IEEE 802.11 wireless LANs

As the acceptance and popularity of wireless networking technologies has proliferated, the security of the IEEE 802.11 wireless local area network (WLAN) has advanced in leaps and bounds. From tenuous beginnings, where the only safe way to deploy a WLAN was to assume it was hostile and employ higherlayer information security controls, to the current state of the art, all manner of improvements have been conceived and many implemented. This work investigates some of the remaining issues surrounding IEEE 802.11 WLAN operation. While the inherent issues in WLAN deployments and the problems of the original Wired Equivalent Privacy (WEP) provisions are well known and widely documented, there still exist a number of unresolved security issues. These include the security of management and control frames and the data link layer protocols themselves. This research introduces a novel proposal to enhance security at the link layer of IEEE 802.11 WLANs and then conducts detailed theoretical and empirical investigation and analysis of the eects of such proposals. This thesis �rst de�nes the state of the art in WLAN technology and deployment, including an overview of the current and emerging standards, the various threats, numerous vulnerabilities and current exploits. The IEEE 802.11i MAC security enhancements are discussed in detail, along with the likely outcomes of the IEEE 802.11 Task Group W1, looking into protected management frames. The problems of the remaining unprotected management frames, the unprotected control frames and the unprotected link layer headers are reviewed and a solution is hypothesised, to encrypt the entire MAC Protocol Data Unit (MPDU), including the MAC headers, not just the MAC Service Data Unit (MSDU) commonly performed by existing protocols. The proposal is not just to encrypt a copy of the headers while still using cleartext addresses to deliver the frame, as used by some existing protocols to support the integrity and authenticity of the headers, but to pass the entire MPDU only as ciphertext to also support the con�dentiality of the frame header information. This necessitates the decryption of every received frame using every available key before a station can determine if it is the intended recipient. As such, this raises serious concerns as to the viability of any such proposal due to the likely impact on throughput and scalability. The bulk of the research investigates the impacts of such proposals on the current WLAN protocols. Some possible variations to the proposal are also provided to enhance both utility and speed. The viability this proposal with respect to the eect on network throughput is then tested using a well known and respected network simulation tool, along with a number of analysis tools developed speci�cally for the data generated here. The simulator's operation is �rst validated against recognised test outputs, before a comprehensive set of control data is established, and then the proposal is tested and and compared against the controls. This detailed analysis of the various simulations should be of bene�t to other researchers who need to validate simulation results. The analysis of these tests indicate areas of immediate improvement and so the protocols are adjusted and a further series of experiments conducted. These �nal results are again analysed in detail and �nal appraisals provided.

Macular function in tilted disc syndrome

Tilted disc syndrome can cause visual field defects due to an optic disc anomaly. Recent electrophysiological findings demonstrate reduced central outer retinal function with ophthalmoscopically normal maculae. We measured macular sensitivity with the microperimeter and performed psychophysical assessment of mesopic rod and cone luminance temporal sensitivity (critical fusion frequency)in a 52-year-old male patient with tilted disc syndrome and ophthalmoscopically normal maculae. We found a marked reduction of sensitivity in the central 20 degrees and reduced rod- and cone-mediated mesopic visual function. Our findings extend previous electrophysiological data that suggest an outer retinal involvement of cone pathways and present a case with rod and cone impairment mediated via the magnocellular pathway in uncomplicated tilted disc syndrome.

Corneal confocal microscopy : a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy

Patients with idiopathic small fibre neuropathy (ISFN) have been shown to have significant intraepidermal nerve fibre loss and an increased prevalence of impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of IGT and additional metabolic risk factors may contribute to small nerve fibre damage in these patients. Twenty-five patients with ISFN and 12 aged-matched control subjects underwent a detailed evaluation of neuropathic symptoms, neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM)) to quantify small nerve fibre pathology. Eight (32%) patients had IGT. Whilst all patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except for warm thresholds were normal. Corneal sensitivity was reduced and CCM demonstrated a significant reduction in corneal nerve fibre density (NFD) (Pb0.0001), nerve branch density (NBD) (Pb0.0001), nerve fibre length (NFL) (Pb0.0001) and an increase in nerve fibre tortuosity (NFT) (Pb0.0001). However these parameters did not differ between ISFN patients with and without IGT, nor did they correlate with BMI, lipids and blood pressure. Corneal confocal microscopy provides a sensitive non-invasive means to detect small nerve fibre damage in patients with ISFN and metabolic abnormalities do not relate to nerve damage.

Contrast enhancement of EPID images via difference imaging : a feasibility study

In this study, the feasibility of difference imaging for improving the contrast of electronic portal imaging device (EPID) images is investigated. The difference imaging technique consists of the acquisition of two EPID images (with and without the placement of an additional layer of attenuating medium on the surface of the EPID)and the subtraction of one of these images from the other. The resulting difference image shows improved contrast, compared to a standard EPID image, since it is generated by lower-energy photons. Results of this study show that, ¯rstly, this method can produce images exhibiting greater contrast than is seen in standard megavoltage EPID images and that, secondly, the optimal thickness of attenuating material for producing a maximum contrast enhancement may vary with phantom thickness and composition. Further studies of the possibilities and limitations of the di®erence imaging technique, and the physics behind it, are therefore recommended.

Hospital beds : A primer for counting and comparing

There is considerable public, political and professional debate about the need for additional hospital beds in Australia. However, there is no clarity in regard to the definition, meaning and significance of hospital bed counts. Relative to population, there has been a total decline in bed availability in Australia over the past 15 years of 14.6% (22.9% for public hospital beds). This decline is partly offset by reductions in length of stay and changes to models of care; however, the net effect is increased bed occupancy which has in turn resulted in system-wide congestion. Future bed capability needs to be better planned to meet growing demands while at the same time continuing trends for more efficient use. Future planning should be based in part on weighted bed capability matched to need.

A national framework for disaster health education in Australia

INTRODUCTION: Recent events have heightened awareness of disaster health issues and the need to prepare the health workforce to plan for and respond to major incidents. This has been reinforced at an international level by the World Association for Disaster and Emergency Medicine, which has proposed an international educational framework. ----------- OBJECTIVE: The aim of this paper is to outline the development of a national educational framework for disaster health in Australia. ----------- METHODS: The framework was developed on the basis of the literature and the previous experience of members of a National Collaborative for Disaster Health Education and Research. The Collaborative was brought together in a series of workshops and teleconferences, utilizing a modified Delphi technique to finalize the content at each level of the framework and to assign a value to the inclusion of that content at the various levels. ----------- FRAMEWORK: The framework identifies seven educational levels along with educational outcomes for each level. The framework also identifies the recommended contents at each level and assigns a rating of depth for each component. The framework is not intended as a detailed curriculum, but rather as a guide for educationalists to develop specific programs at each level. ----------- CONCLUSIONS: This educational framework will provide an infrastructure around which future educational programs in Disaster Health in Australia may be designed and delivered. It will permit improved articulation for students between the various levels and greater consistency between programs so that operational responders may have a consistent language and operational approach to the management of major events.

An electrospun polycaprolactone–collagen membrane for the resurfacing of cartilage defects

A polycaprolactone (PCL)–collagen electrospun mesh is proposed as a novel alternative to the conventional periosteal graft in autologous chondrocyte implantation. This is the first known attempt in designing a cartilage resurfacing membrane using a mechanically resilient PCL mesh with a weight-average molecular weight of 139 300 that is enhanced with bioactive collagen. PCL–collagen 10, 20 and 40% electrospun meshes (Coll-10, Coll-20 and Coll-40) were evaluated and it was discovered that the retention of surface collagen could only be achieved in Coll-20 and Coll-40. Furthermore Coll-20 was stiffer and stronger than Coll-40 and it satisfied the mechanical demands at the cartilage implant site. When seeded with mesenchymal stem cells (MSCs), the cells adhered on the surface of the Coll-20 mesh and they remained viable over a period of 28 days; however, they were unable to infiltrate through the dense meshwork. Cell compatibility was also noted in the chondrogenic environment as the MSCs differentiated into chondrocytes with the expression of Sox9, aggrecan and collagen II. More importantly, the mesh did not induce a hypertrophic response from the cells. The current findings support the use of Coll-20 as a cartilage patch, and future implantation studies are anticipated.

A framework for improved adolescent and child safety in MMOs

This paper presents an approach to providing better safety for adolescents playing online games. We highlight an emerging paedophile presence in online games and offer a general framework for the design of monitoring and alerting tools. Our method is to monitor and detect relationships forming with a child in online games, and alert if the relationship indicates an offline meeting with the child has been arranged or has the potential to occur. A prototype implementation with demonstrative components of the framework has been created and is introduced. The prototype demonstration and evaluation uses a teen rated online relationship-building environment for its case study, specifically the predominant Massive Multiplayer Online Game (MMO) World of Warcraft.

Colonization and osteogenic differentiation of different stem cell sources on electrospun nanofiber meshes

Numerous challenges remain in the successful clinical translation of cell-based therapies for musculoskeletal tissue repair, including the identification of an appropriate cell source and a viable cell delivery system. The aim of this study was to investigate the attachment, colonization, and osteogenic differentiation of two stem cell types, human mesenchymal stem cells (hMSCs) and human amniotic fluid stem (hAFS) cells, on electrospun nanofiber meshes. We demonstrate that nanofiber meshes are able to support these cell functions robustly, with both cell types demonstrating strong osteogenic potential. Differences in the kinetics of osteogenic differentiation were observed between hMSCs and hAFS cells, with the hAFS cells displaying a delayed alkaline phosphatase peak, but elevated mineral deposition, compared to hMSCs. We also compared the cell behavior on nanofiber meshes to that on tissue culture plastic, and observed that there is delayed initial attachment and proliferation on meshes, but enhanced mineralization at a later time point. Finally, cell-seeded nanofiber meshes were found to be effective in colonizing three-dimensional scaffolds in an in vitro system. This study provides support for the use of the nanofiber mesh as a model surface for cell culture in vitro, and a cell delivery vehicle for the repair of bone defects in vivo.

A distributed denial of service testbed

The Denial of Service Testing Framework (dosTF) being developed as part of the joint India-Australia research project for ‘Protecting Critical Infrastructure from Denial of Service Attacks’ allows for the construction, monitoring and management of emulated Distributed Denial of Service attacks using modest hardware resources. The purpose of the testbed is to study the effectiveness of different DDoS mitigation strategies and to allow for the testing of defense appliances. Experiments are saved and edited in XML as abstract descriptions of an attack/defense strategy that is only mapped to real resources at run-time. It also provides a web-application portal interface that can start, stop and monitor an attack remotely. Rather than monitoring a service under attack indirectly, by observing traffic and general system parameters, monitoring of the target application is performed directly in real time via a customised SNMP agent.

Finding a way through the ethical and legal maze : withdrawing medical treatment and euthanasia

This article examines Finnis' and Keown's claim that the intention/foresight distinction should be used as the basis for the lawfulness of withholding and withdrawing medical treatment, rather than the act/omission distinction which is currently used. I argue that whilst the intention/foresight distinction is sound and can apply to palliative pain relief hastening death, it cannot be applied to withholding and withdrawing medical treatment. Instead, the act/omission distinction remains the better basis for the lawfulness of withholding and withdrawal, and law reform is consequently unnecessary.

A CFD study of Hong Kong refuge floor design : floor height effect

Since 1996, ther provision of a refuge floor has been a mandatory feature for all new tall buildings in Hong Kong. These floors are designed to provide for building occupants a fire safe environment that is also free from smoke. However, the desired cross ventilation on these floors to achieve the removal of smoke, assumed by the Building Codes of Hong Kong, is still being questioned so that a further scientific study of the wind-induced ventilation of a refuge fllor is needed. This paper presents an investigation into this issue. The developed computational technique used in this paper was adopted to study the wind-induced natural ventilation on a refuge floor. The aim of the investigation was to establish whether a refuge floor with a cetnral core and having cross ventilation produced by only two open opposite external side walls on the refuge floor would provide the required protection in all situations taking into account behaviour of wind due to different floor heights, wall boundary conditions and turbulence intensity profiles. The results revealed that natural ventilation can be increased by increasng the floor heigh provided the wind angle to the building is less than 90 degrees. The effectiveness of the solution was greatly reduced when the wind was blowing at 90 degrees to the refuge floor opening.

Comparing exercise prescribed with exercise completed : effects of gender and mode of exercise

The purpose of this study was to compare the amount of exercise prescribed with the amount completed between two different modes of training intervention and between the sexes. Thirty-two men (mean age = 39.1 years, body mass index = 32.9 kg · m-2) and women (mean age = 39.6 years, body mass index = 32.1 kg · m-2) were prescribed traditional resistance training or light-resistance circuit training for 16 weeks. Lean mass and fat mass were determined by dual-energy X-ray absorptiometry at weeks 1 and 16. A completion index was calculated to provide a measure of the extent to which participants completed exercise training relative to the amount of exercise prescribed. The absolute amount of exercise completed by the circuit training group was significantly greater than the amount prescribed (P < 0.0001). The resistance training group consistently under-completed relative to the amount prescribed, but the difference was not significant. The completion index for the circuit training group (26 ± 21.7%) was significantly different from that of the resistance training group (-7.4 ± 3.0%). The completion index was not significantly different between men and women in either group. These data suggest that overweight and obese individuals participating in light-resistance circuit training complete more exercise than is prescribed. Men and women do not differ in the extent to which they over- or under-complete prescribed exercise.

Peripheral ocular aberrations in mild and moderate keratoconus

Purpose: To investigate the influence of keratoconus on peripheral ocular aberrations. Methods: Aberrations of 7 mild and 5 moderate keratoconics were determined over a 42°horizontal x 32° vertical visual field with a modified COAS-HD aberrometer. Control data were obtained from an emmetropic group. Results: Most aberrations in keratoconics showed field dependence predominately along the vertical meridian. Mean spherical equivalent M, oblique astigmatism J45 and regular astigmatism J180 refraction components and total root mean square aberrations (excluding defocus) had high magnitudes in the inferior visual field. The rates of change of aberrations were higher in moderate than in mild keratoconics. Coma was the dominant peripheral higher-order aberration in both emmetropes and keratoconics; for the latter it had high magnitudes in the centre and periphery of the visual field. Conclusion: Greater rates of change of aberrations across the visual field occurred for the keratoconic groups than for the emmetropic control group. Moderate keratoconics had more rapid changes in, and higher magnitudes of aberrations across the visual field than mild keratoconics. The dominant higher-order aberration for the keratoconics across the visual field was vertical coma.