Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human C. trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targetted for anti-microbial therapy for intracellular pathogens.

Utilizing Wide-Area Signals for off-center SVCs to damp interarea oscillations

Wide-Area Measurement Systems (WAMS) provide the opportunity of utilizing remote signals from different locations for the enhancement of power system stability. This paper focuses on the implementation of remote measurements as supplementary signals for off-center Static Var Compensators (SVCs) to damp inter-area oscillations. Combination of participation factor and residue method is used for the selection of most effective stabilizing signal. Speed difference of two generators from separate areas is identified as the best stabilizing signal and used as a supplementary signal for lead-lag controller of SVCs. Time delays of remote measurements and control signals is considered. Wide-Area Damping Controller (WADC) is deployed in Matlab Simulink framework and is tested under different operating conditions. Simulation results reveal that the proposed WADC improve the dynamic characteristic of the system significantly.

Reduction of Au3+ ions by activated surface atoms of platinum

In this work it is demonstrated that Pt electrodes can be activated by cathodic polarisation in the hydrogen evolution region which makes it prone to oxidation at potentials below that of bulk oxide formation. When an activated Pt electrode is placed in an aqueous HAuCl4 solution the electroless deposition of Au onto the surface of the electrode is observed and confirmed by cyclic voltammetry and XPS measurements. It is demonstrated that the oxidation of active Pt surface atoms provides the driving force for the spontaneous reduction of Au3+ ions into metallic Au to generate a Pt/Au surface which is highly active for the electro-oxidation of ethanol.

Fabrication of metal-nanoparticle-modified semiconducting copper--and silver--TCNQ materials as substrates for the reduction of chromium (VI) using thiosulfate ions at ambient temperature

The formation of readily recoverable and reusable organic semiconducting Cu- and AgTCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) microstructures decorated with Pt and Pd metallic nanoparticles is described for the effective reduction of CrVI ions in aqueous solution at room temperature using both formic acid and an environmentally friendly thiosulfate reductant. The M-TCNQ (M=metal) materials were formed by electrocrystallisation onto a glassy carbon surface followed by galvanic replacement in the presence of H2PtCl6 or PdCl2 to form the composite material. It was found that loading of the surface with nanoparticles could easily be controlled by changing the metal salt concentration. Significantly, the M-TCNQ substrates facilitated the formation of well-isolated metal nanoparticles on their surfaces under appropriate galvanic replacement conditions. The semiconductor–metal nanoparticle combination was also found to be critical to the catalyst performance, wherein the best-performing material was CuTCNQ modified by well-isolated Pt nanoparticles with both formic acid and thiosulfate ions as the reductant.

Road safety in Australia : successes, challenges for the future, and possibilities for the USA

Overview - Role of CARRS-Q - Australia’s road safety performance - Key features of Australia’s approach to road safety: - Strong reliance on traffic law enforcement, supported by mass media public education - Adoption of the Safe Systems approach - Ambitious road trauma reduction targets? - Ongoing challenges - Possibilities for the USA

New strategy toward dioxin risk reduction for local residents surrounding severe dioxin hotspots in Vietnam

Background A public health intervention program with active involvement of local related stakeholders was piloted in the Bien Hoa dioxin hot spot (2007-2009), and then expanded to the Da Nang dioxin hot spot in Vietnam (2009-2011). It aimed to reduce the risk of dioxin exposure through foods for local residents. This article presents the results of the intervention in Da Nang. Methodology To assess the results of this intervention program, pre-intervention and post-intervention knowledge-attitude-practice (KAP) surveys were implemented in 400 households, randomly selected from four wards surrounding Da Nang Airbase in 2009 and 2011, respectively. Results After the intervention, the knowledge on the existence of dioxin in food, dioxin exposure pathways, potential high risk foods and preventive measures significantly increased (p < 0.05). 98% were willing to follow advice on preventing dioxin exposure. Practices to reduce the risk of dioxin exposure also statistical significantly improved (p<0.05). After intervention, 60.4% of households undertook exposure preventive measures, significantly higher than that of the pre-intervention survey (39.6%; χ2 =40.15 , P<0.001). High risk foods had quite low rates of daily consumption (from 0% to 2.5%) and were significantly reduced (p<0.05). Conclusions This is seen as an effective intervention strategy toward reducing the risk of human exposure to dioxin at dioxin hot spots. While greater efforts are needed for remediating dioxin polluted areas inside airbases, there is also evidence to suggest that, during the past four decades, pollution has been expanding to the surrounding areas. For this reason, this model should be quickly expanded to the remaining dioxin hot spots in Vietnam to further reduce the exposure risk in these areas.

Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer : lessons from the experience of a high-volume center

Objective: Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed. Methods: Three time periods were studied, 1990 to 1998 (period 1), 1999 to 2003 (period 2), and 2004 to 2008 (period 3), in which 471, 254, and 342 patients, respectively, with esophageal cancer were treated with curative intent. All data were prospectively recorded, and staging, pathology, treatment, operative, and oncologic outcomes were compared. Results: Five-year disease-specific survival was 28%, 35%, and 44%, and in-hospital postoperative mortality was 6.7%, 4.4%, and 1.7% for periods 1 to 3, respectively (P < .001). Period 3, compared with periods 1 and 2, respectively, was associated with significantly (P < .001) more early tumors (17% vs 4% and 6%), higher nodal yields (median 22 vs 11 and 18), and a higher R0 rate in surgically treated patients (81% vs 73% and 75%). The use of multimodal therapy increased (P < .05) across time periods. By multivariate analysis, age, T stage, N stage, vascular invasion, R status, and time period were significantly (P < .0001) associated with outcome. Conclusions: Improved survival with localized esophageal cancer in the modern era may reflect an increase of early tumors and optimized staging. Important surgical and pathologic standards, including a higher R0 resection rate and nodal yields, and lower postoperative mortality, were also observed. Copyright © 2012 by The American Association for Thoracic Surgery.

A point prevalence study of cancer nursing practices for managing intravascular devices in an Australian tertiary cancer center

Purpose The use of intravascular devices is associated with a number of potential complications. Despite a number of evidence-based clinical guidelines in this area, there continues to be nursing practice discrepancies. This study aims to examine nursing practice in a cancer care setting to identify nursing practice and areas for improvement respective to best available evidence. Methods A point prevalence survey was undertaken in a tertiary cancer care centre in Queensland, Australia. On a randomly selected day, four nurses assessed intravascular device related nursing practices and collected data using a standardized survey tool. Results 58 inpatients (100%) were assessed. Forty-eight (83%) had a device in situ, comprising 14 Peripheral Intravenous Catheters (29.2%), 14 Peripherally Inserted Central Catheters (29.2%), 14 Hickman catheters (29.2%) and six Port-a-Caths (12.4%). Suboptimal outcomes such as incidences of local site complications, incorrect/inadequate documentation, lack of flushing orders, and unclean/non intact dressings were observed. Conclusions This study has highlighted a number of intravascular device related nursing practice discrepancies compared with current hospital policy. Education and other implementation strategies can be applied to improve nursing practice. Following education strategies, it will be valuable to repeat this survey on a regular basis to provide feedback to nursing staff and implement strategies to improve practice. More research is required to provide evidence to clinical practice with regards to intravascular device related consumables, flushing technique and protocols.

Reduction in the incidence of diabetes lower extremity amputations in Queensland : 2005-2010

Background Lower extremity amputation is a common end stage complication among people with diabetes. Since 2006, the Queensland Diabetes Clinical Network has implemented programs aimed at reducing diabetes-related amputations. The aim of this retrospective observational study was to determine the incidence of diabetes lower extremity amputations in Queensland from 2005 to 2010. Methods Data on all Queensland diabetes-related lower extremity amputation admissions from 2005-2010 was obtained using diabetes amputation-related ICD-10-AM (hospital discharge) codes. Queensland diabetes amputation incidences were calculated for both general and diabetes populations using population data from the Australian Bureau of Statistics and National Diabetes Services Scheme respectively. Chi-squared tests were used to assess changes in amputation incidence over time. Results Overall, 4,443 admissions for diabetes-related amputation occurred; 32% (1,434) were major amputations. The diabetes-related amputation incidence among the general population (per 100,000) reduced by 18% (18.2 in 2005, to 15.0 in 2010, p < 0.001); major amputations decreased by 24% (6.6 to 4.7, p < 0.01). The incidence among the diabetes population (per 1,000) reduced by 40% (6.7 in 2005, to 4.0 in 2010, p < 0.001); major amputations decreased by 45% (2.3 to 1.2, p < 0.001). Conclusion This paper appears to be the first to report a significant reduction in diabetes amputation incidence in an Australian state. This decrease has coincided with the implementation of several diabetes foot clinical programs throughout Queensland. Whilst these results are encouraging in the Australian context, further efforts are required to decrease to levels reported internationally.

Climate change and IMO technical and operational measures for reduction of emissions of greenhouse gas from ships

According to a study conducted by the International Maritime organisation (IMO) shipping sector is responsible for 3.3% of the global Greenhouse Gas (GHG) emissions. The 1997 Kyoto Protocol calls upon states to pursue limitation or reduction of emissions of GHG from marine bunker fuels working through the IMO. In 2011, 14 years after the adoption of the Kyoto Protocol, the Marine Environment Protection Committee (MEPC) of the IMO has adopted mandatory energy efficiency measures for international shipping which can be treated as the first ever mandatory global GHG reduction instrument for an international industry. The MEPC approved an amendment of Annex VI of the 1973 International Convention for the Prevention of Pollution from Ships (MARPOL 73/78) to introduce a mandatory Energy Efficiency Design Index (EEDI) for new ships and the Ship Energy Efficiency Management Plan (SEEMP) for all ships. Considering the growth projections of human population and world trade the technical and operational measures may not be able to reduce the amount of GHG emissions from international shipping in a satisfactory level. Therefore, the IMO is considering to introduce market-based mechanisms that may serve two purposes including providing a fiscal incentive for the maritime industry to invest in more energy efficient manner and off-setting of growing ship emissions. Some leading developing countries already voiced their serious reservations on the newly adopted IMO regulations stating that by imposing the same obligation on all countries, irrespective of their economic status, this amendment has rejected the Principle of Common but Differentiated Responsibility (the CBDR Principle), which has always been the cornerstone of international climate change law discourses. They also claimed that negotiation for a market based mechanism should not be continued without a clear commitment from the developed counters for promotion of technical co-operation and transfer of technology relating to the improvement of energy efficiency of ships. Against this backdrop, this article explores the challenges for the developing counters in the implementation of already adopted technical and operational measures.

IMO technical and operational measures for reduction of emissions of greenhouse gas from ships : perspectives of Asian countries

International shipping is responsible for about 2.7% of the global emissions of CO2. In the absence of proper action, emissions from the maritime sector may grow by 150% to 250% by 2050, in comparison with the level of emissions in 2007. Against this backdrop, the International Maritime Organisation has introduced a mandatory Energy Efficiency Design Index (EEDI) for new ships and the Ship Energy Efficiency Management Plan (SEEMP) for all ships. Some Asian countries have voiced serious reservations about the newly adopted IMO regulations. They have suggested that imposing the same obligations on all countries, irrespective of their economic status, is a serious departure from the Principle of Common but Differentiated Responsibility, which has always been the cornerstone of international climate change law discourse. Against this backdrop, this article presents a brief overview of the technical and operational measures from the perspective of Asian countries.

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

Large-scale analysis of formations in soccer

Due to the demand for better and deeper analysis in sports, organizations (both professional teams and broadcasters) are looking to use spatiotemporal data in the form of player tracking information to obtain an advantage over their competitors. However, due to the large volume of data, its unstructured nature, and lack of associated team activity labels (e.g. strategic/tactical), effective and efficient strategies to deal with such data have yet to be deployed. A bottleneck restricting such solutions is the lack of a suitable representation (i.e. ordering of players) which is immune to the potentially infinite number of possible permutations of player orderings, in addition to the high dimensionality of temporal signal (e.g. a game of soccer last for 90 mins). Leveraging a recent method which utilizes a "role-representation", as well as a feature reduction strategy that uses a spatiotemporal bilinear basis model to form a compact spatiotemporal representation. Using this representation, we find the most likely formation patterns of a team associated with match events across nearly 14 hours of continuous player and ball tracking data in soccer. Additionally, we show that we can accurately segment a match into distinct game phases and detect highlights. (i.e. shots, corners, free-kicks, etc) completely automatically using a decision-tree formulation.

Voltammetric, spectroscopic, and microscopic investigations of electrocrystallized forms of semiconducting AgTCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) exhibiting different morphologies and colors

Chemically synthesized AgTCNQ exists in two forms that differ in their morphologies (needles and microcrystals) and colors (red and blue). It is now shown that both forms exhibit essentially indistinguishable X-ray diffraction, spectroscopic, and thermochemical data, implying that they are not separate phases, as implied in some literature. Electrochemical reduction of TCNQ((MeCN)) in the presence of Ag+((MeCN)) generates both red and blue AgTCNQ. On glassy carbon, platinum, or indium tin oxide electrodes and at relatively positive deposition potentials, slow growth of high aspect ratio, red needle AgTCNQ crystals occurs. After longer times and at more negative deposition potentials, blue microcrystalline AgTCNQ thin films are favored. Blue AgTCNQ is postulated to be generated via reduction of a Ag+\[(TCNQ(center dot-))(TCNQ)]((MeCN)) intermediate. At even more negative potentials, Ag-(metal) formation inhibits further growth of AgTCNQ. On a gold electrode, Ag-(metal)) deposition occurs at more positive potentials than on the other electrode materials examined. However, surface plasmon resonance data indicate (hat a small potential region is available between the stripping of Ag-(metal)) and the oxidation of TCNQ(center dot-)(MeCN) back to TCNQ(MeCN) where AgTCNQ may form. AgTCNQ in both the red and blue forms also can be prepared electrochemically on a TCNQ((s)) modified electrode in -0.1 M AgNO3(aq) where deposition of Ag(m,,,I) onto the TCNQ((s)) crystals allows a charge transfer process to occur. However, the morphology formed in this solid-solid phase transformation is more difficult to control.

Voltage unbalance reduction in low voltage feeders by dynamic switching of residential customers among three phases

Low voltage distribution feeders with large numbers of single phase residential loads experience severe current unbalance that often causes voltage unbalance problems. The addition of intermittent generation and new loads in the form of roof top photovoltaic generation and electric vehicles makes these problems even more acute. In this paper, an intelligent dynamic residential load transfer scheme is proposed. Residential loads can be transferred from one phase to another phase to minimize the voltage unbalance along the feeder. Each house is supplied through a static transfer switch with three-phase input and single-phase output connection. The main controller, installed at the transformer will observe the power consumption in each load and determine which house(s) should be transferred from one phase to another in order to keep the voltage unbalance in the feeder at a minimum. The efficacy of the proposed load transfer scheme is verified through MATLAB and PSCAD/EMTDC simulations.