Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I.

A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication. Specifically it has been reported that purified virus particles have topo I activity and that inhibitors of this enzyme can inhibit virus replication in vitro. We have investigated a possible association of HIV-1 gag proteins with topo I activity. We found that whereas the gag-encoded proteins by themselves do not have activity, the nucleocapsid protein p15 can interact with and enhance the activity of cellular topo I. Furthermore it could be demonstrated that topo I markedly enhanced HIV-1 reverse transcriptase activity in vitro and that this could be inhibited by the topo I-specific inhibitor camptothecin. The findings suggest that cellular topo I plays an important role in the reverse transcription of HIV-1 RNA and that the recruitment of this enzyme may be an important step in virus replication.

Identification of key temperature measurement technologies for the enhancement of product and equipment integrity in the light controlled factory

Thermal effects in uncontrolled factory environments are often the largest source of uncertainty in large volume dimensional metrology. As the standard temperature for metrology of 20°C cannot be achieved practically or economically in many manufacturing facilities, the characterisation and modelling of temperature offers a solution for improving the uncertainty of dimensional measurement and quantifying thermal variability in large assemblies. Technologies that currently exist for temperature measurement in the range of 0-50°C have been presented alongside discussion of these temperature measurement technologies' usefulness for monitoring temperatures in a manufacturing context. Particular aspects of production where the technology could play a role are highlighted as well as practical considerations for deployment. Contact sensors such as platinum resistance thermometers can produce accuracy closest to the desired accuracy given the most challenging measurement conditions calculated to be ∼0.02°C. Non-contact solutions would be most practical in the light controlled factory (LCF) and semi-invasive appear least useful but all technologies can play some role during the initial development of thermal variability models.

Pharmacological enhancement of naltrexone treatment for opioid dependence: a review.

PURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with increasing social costs that requires expanding treatment beyond opioid agonist substitution. The opioid antagonist naltrexone has displayed a remarkable association of theoretical effectiveness and poor clinical utility in treating OD due to noncompliant behavior and low acceptability among patients, only partly modified by psychosocial interventions. We reviewed pharmacological studies, including naltrexone depot formulations and combination treatments. METHOD: We searched PubMed for clinical studies on the use of naltrexone implants and slow-release injections in OD, and investigations using adjunct medications to improve naltrexone maintenance therapy of OD. We discussed the results in view of their application to the clinical practice. RESULTS: Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations, some of which are controlled clinical trials. Pilot investigations have gathered initial positive results on the use of naltrexone in combination with serotonin reuptake inhibitors, α-2 adrenergic, opioid, and γ-aminobutyric acid agonist medications. CONCLUSION: Current evidence suggests that more research on effectiveness and safety is needed in support of depot naltrexone treatment for OD. Further research comparing slow-release with oral naltrexone and opioid agonist medications will help characterize the role of opioid antagonist-mediated treatment of OD. Preliminary investigations on naltrexone combination treatments suggest the opportunity to continue study of new mixed receptor activities for the treatment of OD and other drug addictions.

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Power sharing and stability enhancement of an autonomous microgrid with inertial and non-inertial DGs with DSTATCOM

This paper proposes a method of enhancing system stability with a distribution static compensator (DSTATCOM) in an autonomous microgrid with multiple distributed generators (DG). It is assumed that there are both inertial and non-inertial DGs connected to the microgrid. The inertial DG can be a synchronous machine of smaller rating while inertia less DGs (solar) are assumed as DC sources. The inertia less DGs are connected through Voltage Source Converter (VSC) to the microgrid. The VSCs are controlled by either state feedback or current feedback mode to achieve desired voltage-current or power outputs respectively. The power sharing among the DGs is achieved by drooping voltage angle. Once the reference for the output voltage magnitude and angle is calculated from the droop, state feedback controllers are used to track the reference. The angle reference for the synchronous machine is compared with the output voltage angle of the machine and the error is fed to a PI controller. The controller output is used to set the power reference of the synchronous machine. The rate of change in the angle in a synchronous machine is restricted by the machine inertia and to mimic this nature, the rate of change in the VSCs angles are restricted by a derivative feedback in the droop control. The connected distribution static compensator (DSTATCOM) provides ride through capability during power imbalance in the microgrid, especially when the stored energy of the inertial DG is not sufficient to maintain stability. The inclusion of the DSATCOM in such cases ensures the system stability. The efficacies of the controllers are established through extensive simulation studies using PSCAD.

Developing an integrated decision model for the enhancement of sustainability deliverables for Australian road infrastructure projects

Road and highway infrastructure provides the backbone for a nation's economic growth. The versatile dispersion of population in Australia, from sparsely settled communities in remote areas to regenerated inner city suburbs with high density living in metropolitans, calls for continuing development and improvement on roads infrastructure under the current federal government policies and state governments' strategic plans. As road infrastructure projects involve large resources and mechanism, achieving sustainability not only in economic scales but also through environmental and social responsibility becomes a crucial issue. Current efforts are often impeded by different interpretation on sustainability agenda by stakeholders involved in these types of projects. As a result, sustainability deliverables at the project level is not often as transparent and measurable, compared to promises in project briefs and designs. This paper reviews the past studies on sustainable infrastructure construction, focusing on roads and highway projects. Through literature study and consultation with the industry, key sustainability indicators specific to road infrastructure projects have been identified. Based on these findings, this paper introduces an on-going research project aimed at identifying and integrating the different perceptions and priority needs of the stakeholders, and issues that impact on the gap between sustainability foci and its actual realization at project end level. The exploration helps generate an integrated decision-making model for sustainable road infrastructure projects. The research will promote to the industry more systematic and integrated approaches to decision-making on the implementation of sustainability strategies to achieve deliverable goals throughout the development and delivery process of road infrastructure projects in Australia.

Simulation and enhancement of a cardiovascular device test rig

Cardiovascular assist devices are tested in mock circulation loops (MCLs) prior to animal and clinical testing. These MCLs rely on characteristics such as pneumatic parameters to create pressure and flow, and pipe dimensions to replicate the resistance, compliance and fluid inertia of the natural cardiovascular system. A mathematical simulation was developed in SIMULINK to simulate an existing MCL. Model validation was achieved by applying the physical MCL characteristics to the simulation and comparing the resulting pressure traces. These characteristics were subsequently altered to improve and thus predict the performance of a more accurate physical system. The simulation was successful in simulating the physical mock circulation loop, and proved to be a useful tool in the development of improved cardiovascular device test rigs.

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.