Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder

Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Vibrational spectroscopy of the sulphate mineral sturmanite from Kuruman manganese deposits, South Africa

The mineral sturmanite is a hydrated calcium iron aluminium manganese sulphate tetrahydroxoborate hydroxide of formula Ca6(Fe, Al, Mn)2(SO4)2(B(OH)4)(OH)12•26H2O. We have studied the mineral sturmanite using a number of techniques, including SEM with EPMA and vibrational spectroscopy. Chemical analysis shows a homogeneous phase, composed by Ca, Fe, Mn, S, Al and Si. B is not determined in this EPMA technique. An intense Raman band at 990 cm−1 is assigned to the SO42− symmetric stretching mode. Raman spectroscopy identifies multiple sulphate symmetric stretching modes in line with the three sulphate crystallographically different sites. Raman spectroscopy also identifies a band at 1069 cm−1 which may be attributed to a carbonate symmetric stretching mode, indicating the presence of thaumasite. Infrared spectra display two bands at 1080 and 1107 cm−1 assigned to the SO42− antisymmetric stretching modes. The observation of multiple bands in this ν4 spectral region offers evidence for the reduction in symmetry of the sulphate anion from Td to C2v or even lower symmetry. The Raman band at 3622 cm−1 is assigned to the OH unit stretching vibration and the broad feature at around 3479 cm−1 to water stretching bands. Infrared spectroscopy shows a set of broad overlapping bands in the OH stretching region. Vibrational spectroscopy enables an assessment of the molecular structure of sturmanite to be made.

Wet tropics reef rescue impact report 2009

The Wet Tropics region has a unique water asset and is also considered a priority region for the improvement of water quality entering the Great Barrier Reef due to a combination of high rainfall, intensive agricultural use, urban areas and the proximity of valuable reef assets to the coast. Agricultural activities are one of many identified threats to water quality and water flows in the Wet Tropics in terms of sediment and pollutant-related water quality decline. Information describing the current state of agricultural management practices across the region is patchy at best. Based on the best available information on agricultural management practices in the Wet Tropics in 2008, it is clear that opportunities exist to improve nutrient, sediment and pesticide management practice to reduce the impact on the water asset and the Great Barrier Reef. Based on current understandings of practices and the relationship between practices and reef water quality, the greatest opportunities for improved water quality are as follows: · nutrients – correct rate and the placement of fertilisers; · pesticides – improve weed control planning, herbicide rates and calibration practice; and · soil and sediment – implement new farming system practices. The 2008-09 Reef Rescue program sought to accelerate the rate of adoption of improved management practices and through Terrain invested $6.8M in the 2008-09 year for: · landholder water quality improvement incentive payments; · cross regional catchment repair of wetlands and riparian lands in areas of high sediment or nutrient loss; and · partnerships in the region to lever resources and support for on-ground practice change. The program delivered $3,021,999 in onground incentives to landholders in the Wet Tropics to improve farm practices from D or C level to B or A level. The landholder Water Quality Incentives Grants program received 300 individual applications for funding and funded 143 individual landholders to implement practice change across 36,098 ha of farm land. It is estimated that the Reef Rescue program facilitated practice change across 21% of the cane industry, and 20% of the banana industry. The program levered an additional $2,441,166 in landholder cash contributions and a further $907,653 in non-cash in-kind contributions bringing the total project value of the landholder grants program in the Wet Tropics to $6,370,819. Most funded projects targeted multiple water quality objectives with a focus on nutrient and sediment reduction. Of the 143 projects funded, 115 projects addressed nutrient management either as the primary focus or in combination with strategies that targeted other water quality objectives. Overall, 82 projects addressed two or more water quality targets. Forty-five percent of incentive funds were allocated to new farming system practices (direct drill legumes, zonal tillage equipment, permanent beds, min till planting equipment, GPS units, laser levelling), followed by 24% allocated to subsurface fertiliser applicators (subsurface application of fertiliser using a stool splitter or beside the stool, at the correct Six Easy Steps rate). As a result, Terrain estimates that the incentive grants achieved considerable reductions in nitrogen, phosphorus, sediment and pesticide loads. The program supported nutrient management training of 167 growers managing farms covering over 20% of the area harvested in 2008, and 18 industry advisors and resellers. This resulted in 115 growers (155 farms) developing nutrient management plans. The program also supported Integrated Weed Management training of 80 growers managing farms covering 8% of the area harvested in 2008, and 6 industry advisors and resellers. This report, which draws on the best available Reef Rescue Management Monitoring, Evaluation, Reporting, and Improvement (MERI) information to evaluate program performance and impact on water quality outcomes, is the first in a series of annual reports that will assess and evaluate the impact of the Reef Rescue program on agricultural practices and water quality outcomes. The assessment is predominantly focused on the cane industry because of data availability. In the next stage, efforts will expand to: · improve practice data for the banana and grazing industry; · gain a better understanding of the water quality trends and the factors influencing them in the Wet Tropics; in particular work will focus on linking the results of the Paddock to Reef monitoring program and practice change data to assess program impact; · enhance estimations of the impact of practice change on pollutant loads from agricultural land use; · gain a better understanding of the extent of ancillary practice (change not directly funded) resulting from Reef Rescue training/ education/communication programs; and · provide a better understanding of the economic cost of practice change across the Wet Tropics region. From an ecological perspective, water quality trends and the factors that may be contributing to change, require further investigation. There is a critical need to work towards an enhanced understanding of the link between catchment land management practice change and reef water quality, so that reduced nutrient, sediment, and pesticide discharge to the Great Barrier Reef can be quantified. This will also assist with future prioritisation of grants money to agricultural industries, catchments and sub catchments. From a social perspective, the program has delivered significant water quality benefits from landholder education and training. It is believed that these activities are giving landholders the information and tools to implement further lasting change in their production systems and in doing so, creating a change in attitude that is supportive and inclusive of Natural Resource Management (NRM). The program in the Wet Tropics has also considerably strengthened institutional partnerships for NRM, particularly between NRM and industry and extension organisations. As a result of the Reef Rescue program, all institutions are actively working together to collectively improve water quality. The Reef Rescue program is improving water quality entering the Great Barrier Reef Lagoon by catalysing substantial activity in the Wet Tropics region to improve land management practices and reduce the water quality impact of agricultural landscapes. The solid institutional partnerships between the regional body, industry, catchment and government organisations have been fundamental to the successful delivery of the landholder grant and catchment rehabilitation programs. Landholders have generally had a positive perception and reaction to the program, its intent, and the practical, focused nature of grant-based support. Demand in the program was extremely high in 2008-09 and is expected to increase in 2009-2010.

Improved procedures for business accommodation on transportation construction projects

Highway construction projects have direct impacts on adjacent businesses. The nature and the degree of impact depend on individual business characterization and project specific factors. The type of business is also a relevant factor in predicting the impact of transportation construction projects. This paper presents the results of research focused on developing an in-depth understanding of these relationships. The study includes project case studies of three transportation construction projects in Florida. Surveys were conducted with all adjacent businesses, which were combined with analyses of the business accommodation procedures employed by State Highway Agencies (SHAs) nationwide to provide measure the efficiency of present rules. The results include an analysis of differing priorities for different classification of businesses and development of design and construction management best practices to better accommodate businesses during highway construction. A pilot project that employed business accommodation principles devised in this research, and improvements to business accommodations observed were compared to cases where no measures were taken.

Plasma-produced phase-pure cuprous oxide nanowires for methane gas sensing

Phase-selective synthesis of copper oxide nanowires is warranted by several applications, yet it remains challenging because of the narrow windows of the suitable temperature and precursor gas composition in thermal processes. Here, we report on the room-temperature synthesis of small-diameter, large-area, uniform, and phase-pure Cu2O nanowires by exposing copper films to a custom-designed low-pressure, thermally non-equilibrium, high-density (typically, the electron number density is in the range of 10 11-1013cm-3) inductively coupled plasmas. The mechanism of the plasma-enabled phase selectivity is proposed. The gas sensors based on the synthesized Cu2O nanowires feature fast response and recovery for the low-temperature (∼140°C) detection of methane gas in comparison with polycrystalline Cu2O thin film-based gas sensors. Specifically, at a methane concentration of 4%, the response and the recovery times of the Cu2O nanowire-based gas sensors are 125 and 147s, respectively. The Cu2O nanowire-based gas sensors have a potential for applications in the environmental monitoring, chemical industry, mining industry, and several other emerging areas.

Composition-dependent structural and electronic properties of α-(Si1−xCx)3N4

The highly unusual structural and electronic properties of the α-phase of (Si1-xCx)3N4 are determined by density functional theory (DFT) calculations using the Generalized Gradient Approximation (GGA). The electronic properties of α-(Si 1-xCx)3N4 are found to be very close to those of α-C3N4. The bandgap of α-(Si 1-xCx)3N4 significantly decreases as C atoms are substituted by Si atoms (in most cases, smaller than that of either α-Si3N4 or α-C3N4) and attains a minimum when the ratio of C to Si is close to 2. On the other hand, the bulk modulus of α-(Si1-xCx)3N 4 is found to be closer to that of α-Si3N 4 than of α-C3N4. Plasma-assisted synthesis experiments of CNx and SiCN films are performed to verify the accuracy of the DFT calculations. TEM measurements confirm the calculated lattice constants, and FT-IR/XPS analysis confirms the formation and lengths of C-N and Si-N bonds. The results of DFT calculations are also in a remarkable agreement with the experiments of other authors.

Pro bono partnerships in environmental law : enhancing outcomes for universities and CLCs

CLE can be a life-changing event in a law student’s education. It can open their eyes to the day-to-day operation of justice and provide them with examples of possible career paths they may never have thought existed. Yet it can also provide long-term benefits for CLCs and academics. Recent CLE models have moved towards partnerships with external organisations and away from on-site legal clinics. Some examples have exhibited success with a multidisciplinary approach involving students from non-law disciplines to provide a holistic approach to a CLC’s needs. Such a multidisciplinary approach is of particular benefit in community lawyering clinics where students are engaged in social change lawyering. The QUT/EDO partnership presents a new model in the environmental clinic landscape in Australia. Initial feedback suggests that the clinic has assisted students in gaining insight into the access to justice issues arising from mining activities and to raise the level of understanding and awareness among community members of their legal rights to protect the environment. Looking at ways to increase partnerships between universities and CLCs is of vital importance in the future, given recent federal government CLC funding cuts. The legal clinic model has great potential to evolve and contribute in ensuring the continued operation of legal initiatives to protect the environment in the public interest.

Literacy, poverty and schooling : what matters in young people's education?

This paper draws upon several decades of literacy research in schools in high poverty environments to explore what matters in young people’s education. In dialogue with themes from Kevin Marjoribanks’ work, such as student aspirations, family environments, and teacher expectations, key insights are summarised. Referring to longitudinal case studies and a current ethnographic project, the interplay between literacy, poverty and schooling, and, young people’s aspirations and education outcomes is explored. While the work of educators in high poverty communities continues to be highly demanding, there are some schools and teachers making a durable positive difference to learner dispositions and literate repertoires. Teacher expectations and discursive practices are crucial in this process.

Abundance and prevalence of Aedes aegypti immatures and relationships with household water storage in rural areas in southern Viet Nam

Since 2000, the Government of Viet Nam has committed to provide rural communities with increased access to safe water through a variety of household water supply schemes (wells, ferrocement tanks and jars) and piped water schemes. One possible, unintended consequence of these schemes is the concomitant increase in water containers that may serve as habitats for dengue mosquito immatures, principally Aedes aegypti. To assess these possible impacts we undertook detailed household surveys of Ae. aegypti immatures, water storage containers and various socioeconomic factors in three rural communes in southern Viet Nam. Positive relationships between the numbers of household water storage containers and the prevalence and abundance of Ae. aegypti immatures were found. Overall, water storage containers accounted for 92–97% and 93–96% of the standing crops of III/IV instars and pupae, respectively. Interestingly, households with higher socioeconomic levels had significantly higher numbers of water storage containers and therefore greater risk of Ae. aegypti infestation. Even after provision of piped water to houses, householders continued to store water in containers and there was no observed decrease in water storage container abundance in these houses, compared to those that relied entirely on stored water. These findings highlight the householders’ concerns about the limited availability of water and their strong behavoural patterns associated with storage of water. We conclude that household water storage container availability is a major risk factor for infestation with Ae. aegypti immatures, and that recent investment in rural water supply infrastructure are unlikely to mitigate this risk, at least in the short term.

UNICEF, Jakarta, Indonesia : Review of Satap Schools

A. Background and context 1. Education, particularly basic education (grades1-9), has been considered critical to promoting national economic growth and social well being1. Three factors that con-tribute to the above are: (i) Education increases human capital inherent in a labor force and thus increases productivity. It also increases capacity for working with others and builds community consensus to support national development. (ii) Education can in-crease the innovative capacity of a community to support social and economic growth—use of new technologies, products and services to promote growth and wellbeing. (iii) Education can facilitate knowledge transfer needed to understand the social and eco-nomic innovations and new processes, practices and values. Cognizant of the above benefits of education, the Millennium Development Goals (MDG) and the Education for All (EFA) declarations advocating universal basic education were formulated and ratified by UN member countries. 2. Achieving universal primary education (grade 6) may not be sufficient to maxim-ize the above noted socio-economic and cultural benefits. There is general consensus that basic literacy and numeracy up to grade 9 are essential foundational blocks for any good education system to support national development. Basic Education provides an educational achievement threshold that ensures the learning is retained. To achieve this, the donor partner led interventions and the UN declarations such as the MDG goals have sought universal access to basic education (grades 1-9). As many countries progress towards achieving the universal access targets, recent research evidence suggests that we need more than just access to basic education to impact on the na-tional development. Measuring basic education completion cycle, gross enrolment rate (GER) and participation rate etc., has to now include a focus on quality and relevance of the education2. 3. While the above research finding is generally accepted by the Government of In-donesia (GoI), unlike many other developing countries, Indonesia is geographically and linguistically complex and has the fourth largest education sector in the world. It has over 3000 islands, 17,000 ethnic groups and it takes as long as 7 hours to travel from east to west of the country and has multiple time differences. The education system has six years of primary education (grades 1-6), 3 years of junior secondary education (grades 7-9) and three years of senior secondary education (grades 10-12). Therefore, applying the findings of the above cited research in a country like Indonesia is a chal-lenge. Nevertheless, since the adoption of the National Education Law (2003)3 the GoI has made significant progress in improving access to and quality of basic education (grades 1-9). The 2011/12 national education statistics show the primary education (grades 1-6) completion rate was 99.3%, the net enrolment rate (NER) was 95.4% and the GER was 115.4%. This is a significant achievement considering the complexities faced within Indonesia. This increase in the primary education sub-sector, however, has not flowed onto the Junior Secondary School (JSS) education. The transition from pri-mary to JSS is still short of the GoI targets. In 2012, there were 146,826 primary schools feeding into 33,668 junior secondary schools. The transition rate from primary to secondary in 2011/12 was 78%. When considering district or sub-district level data the transition in poor districts could be less than the aggregated national rate. Poverty and lack of parents’ education, confounded by opportunity cost, are major obstacles to transitioning to JSS4. 4. Table 1 presents a summary of GoI initiatives to accelerate the transition to JSS. GoI, with assistance from the donor community, has built 2465 new regular JSS, mak-ing the total number of regular JSS 33,668. In addition, 57,825 new classrooms have been added to existing regular JSS. Also, in rural and remote areas 4136 Satu-Atap5 (SATAP) schools were built to increase access to JSS. These SATAP schools are the focus of this study as they provide education opportunities to the most marginalized, ru-ral, remote children who otherwise would not have access to JSS and consequently not complete basic education.

Controlling the surface roughness of epitaxial SiC on silicon

The surface of cubic silicon carbide (3C-SiC) hetero-epitaxial films grown on the (111) surface of silicon is a promising template for the subsequent epitaxial growth of III-V semiconductor layers and graphene. We investigate growth and post-growth approaches for controlling the surface roughness of epitaxial SiC to produce an optimal template. We first explore 3C-SiC growth on various degrees of offcut Si(111) substrates, although we observe that the SiC roughness tends to worsen as the degree of offcut increases. Hence we focus on post-growth approaches available on full wafers, comparing chemical mechanical polishing (CMP) and a novel plasma smoothening process. The CMP leads to a dramatic improvement, bringing the SiC surface roughness down to sub-nanometer level, though removing about 200 nm of the SiC layer. On the other hand, our proposed HCl plasma process appears very effective in smoothening selectively the sharpest surface topography, leading up to 30% improvement in SiC roughness with only about 50 nm thickness loss. We propose a simple physical model explaining the action of the plasma smoothening.

Encapsulation of Hydrocortisone and Mesalazine in Zein Microparticles

Zein was investigated for use as an oral-drug delivery system by loading prednisolone into zein microparticles using coacervation. To investigate the adaptability of this method to other drugs, zein microparticles were loaded with hydrocortisone, which is structurally related to prednisolone; or mesalazine, which is structurally different having a smaller LogP and ionizable functional groups. Investigations into the in vitro digestibility, and the electrophoretic profile of zein, and zein microparticles were conducted to shed further insight on using this protein as a drug delivery system. Hydrocortisone loading into zein microparticles was comparable with that reported for prednisolone, but mesalazine loading was highly variable. Depending on the starting quantities of hydrocortisone and zein, the average amount of microparticles equivalent to 4 mg hydrocortisone, (a clinically used dose), ranged from 60-115 mg, which is realistic and practical for oral dosing. Comparatively, an average of 2.5 g of microparticles was required to deliver 250 mg of mesalazine (a clinically used dose), so alternate encapsulation methods that can produce higher and more precise mesalazine loading are required. In vitro protein digestibility revealed that zein microparticles were more resistant to digestion compared to the zein raw material, and that individual zein peptides are not preferentially coacervated into the microparticles. In combination, these results suggest that there is potential to formulate a delivery system based on zein microparticles made using specific subunits of zein that is more resistant to digestion as starting material, to deliver drugs to the lower gastrointestinal tract.

Age, physical inactivity, obesity, health conditions, and health-related quality of life among patients receiving conservative management for musculoskeletal disorders

Background Musculoskeletal conditions and insufficient physical activity have substantial personal and economic costs among contemporary aging societies. This study examined the age distribution, comorbid health conditions, body mass index (BMI), self-reported physical activity levels, and health-related quality of life of patients accessing ambulatory hospital clinics for musculoskeletal disorders. The study also investigated whether comorbidity, BMI, and self-reported physical activity were associated with patients’ health-related quality of life after adjusting for age as a potential confounder. Methods A cross-sectional survey was undertaken in three ambulatory hospital clinics for musculoskeletal disorders. Participants (n=224) reported their reason for referral, age, comorbid health conditions, BMI, physical activity levels (Active Australia Survey), and health-related quality of life (EQ-5D). Descriptive statistics and linear modeling were used to examine the associations between age, comorbidity, BMI, intensity and duration of physical activity, and health-related quality of life. Results The majority of patients (n=115, 51.3%) reported two or more comorbidities. In addition to other musculoskeletal conditions, common comorbidities included depression (n=41, 18.3%), hypertension (n=40, 17.9%), and diabetes (n=39, 17.4%). Approximately one-half of participants (n=110, 49.1%) self-reported insufficient physical activity to meet minimum recommended guidelines and 150 (67.0%) were overweight (n=56, 23.2%), obese (n=64, 28.6%), severely obese (n=16, 7.1%), or very severely obese (n=14, 6.3%), with a higher proportion of older patients affected. A generalized linear model indicated that, after adjusting for age, self-reported physical activity was positively associated (z=4.22, P<0.001), and comorbidities were negatively associated (z=-2.67, P<0.01) with patients’ health-related quality of life. Conclusion Older patients were more frequently affected by undesirable clinical attributes of comorbidity, obesity, and physical inactivity. However, findings from this investigation are compelling for the care of patients of all ages. Potential integration of physical activity behavior change or other effective lifestyle interventions into models of care for patients with musculoskeletal disorders is worthy of further investigation.