PTRF/cavin-1 neutralizes non-caveolar caveolin-1 microdomains in prostate cancer

Caveolin-1 has a complex role in prostate cancer and has been suggested to be a potential biomarker and therapeutic target. As mature caveolin-1 resides in caveolae, invaginated lipid raft domains at the plasma membrane, caveolae have been suggested as a tumor-promoting signaling platform in prostate cancer. However, caveola formation requires both caveolin-1 and cavin-1 (also known as PTRF; polymerase I and transcript release factor). Here, we examined the expression of cavin-1 in prostate epithelia and stroma using tissue microarray including normal, non-malignant and malignant prostate tissues. We found that caveolin-1 was induced without the presence of cavin-1 in advanced prostate carcinoma, an expression pattern mirrored in the PC-3 cell line. In contrast, normal prostate epithelia expressed neither caveolin-1 nor cavin-1, while prostate stroma highly expressed both caveolin-1 and cavin-1. Utilizing PC-3 cells as a suitable model for caveolin-1-positive advanced prostate cancer, we found that cavin-1 expression in PC-3 cells inhibits anchorage-independent growth, and reduces in vivo tumor growth and metastasis in an orthotopic prostate cancer xenograft mouse model. The expression of α-smooth muscle actin in stroma along with interleukin-6 (IL-6) in cancer cells was also decreased in tumors of mice bearing PC-3-cavin-1 tumor cells. To determine whether cavin-1 acts by neutralizing caveolin-1, we expressed cavin-1 in caveolin-1-negative prostate cancer LNCaP and 22Rv1 cells. Caveolin-1 but not cavin-1 expression increased anchorage-independent growth in LNCaP and 22Rv1 cells. Cavin-1 co-expression reversed caveolin-1 effects in caveolin-1-positive LNCaP cells. Taken together, these results suggest that caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression. Cavin-1 expression attenuates the effects of non-caveolar caveolin-1 microdomains partly via reduced IL-6 microenvironmental function. With circulating caveolin-1 as a potential biomarker for advanced prostate cancer, identification of the molecular pathways affected by cavin-1 could provide novel therapeutic targets.

A non-linear interface element model for thin layer high adhesive mortared masonry

A nonlinear interface element modelling method is formulated for the prediction of deformation and failure of high adhesive thin layer polymer mortared masonry exhibiting failure of units and mortar. Plastic flow vectors are explicitly integrated within the implicit finite element framework instead of relying on predictor–corrector like approaches. The method is calibrated using experimental data from uniaxial compression, shear triplet and flexural beam tests. The model is validated using a thin layer mortared masonry shear wall, whose experimental datasets are reported in the literature and is used to examine the behaviour of thin layer mortared masonry under biaxial loading.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults

Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to ‘schizophrenia-like’ cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter : total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.

The effect of the addition of hip strengthening exercises to a lumbopelvic exercise programme for the treatment of non-specific low back pain : a randomized controlled trial

Objectives To compare the efficacy of two exercise programs in reducing pain and disability for individuals with non-specific low back pain and to examine the underlying mechanical factors related to pain and disability for individuals with NSLBP. Design A single-blind, randomized controlled trial. Methods: Eighty participants were recruited from eleven community-based general medical practices and randomized into two groups completing either a lumbopelvic motor control or a combined lumbopelvic motor control and progressive hip strengthening exercise therapy program. All participants received an education session, 6 rehabilitation sessions including real time ultrasound training, and a home based exercise program manual and log book. The primary outcomes were pain (0-100mm visual analogue scale), and disability (Oswestry Disability Index V2). The secondary outcomes were hip strength (N/kg) and two-dimensional frontal plane biomechanics (°) measure during the static Trendelenburg test and while walking. All outcomes were measured at baseline and at 6-week follow up. Results There was no statistical difference in the change in pain (xˉ = -4.0mm, t= -1.07, p =0.29, 95%CI -11.5, 3.5) or disability (xˉ = -0.3%, t= -0.19, p =0.85, 95%CI -3.5, 2.8) between groups. Within group comparisons revealed clinically meaningful reductions in pain for both Group One (xˉ =-20.9mm, 95%CI -25.7, -16.1) and Group Two (xˉ =-24.9, 95%CI -30.8, -19.0). Conclusion Both exercise programs had similar efficacy in reducing pain. The addition of hip strengthening exercises to a motor control exercise program does not appear to result in improved clinical outcome for pain for individuals with non-specific low back pain.

A model to estimate the durability performance of both normal and light-weight concrete

There has been an increasing focus on the development of test methods to evaluate the durability performance of concrete. This paper contributes to this focus by presenting a study that evaluates the effect of water accessible porosity and oven-dry unit weight on the resistance of both normal and light-weight concrete to chloride-ion penetration. Based on the experimental results and regression analyses, empirical models are established to correlate the total charge passed and the chloride migration coefficient with the basic properties of concrete such as water accessible porosity, oven dry unit weight, and compressive strength. These equations can be broadly applied to both normal and lightweight aggregate concretes. The model was also validated by an independent set of experimental results from two different concrete mixtures. The model provides a very good estimate on the concrete’s durability performance in respect to the resistance to chloride ion penetration.

Learnings, case studies and guidelines for establishing shared and collaborative service delivery in the non-government sector: Evaluation of the Multi-Tenant Service Centre (MTSC) Pilots Project

This report presents learnings, case studies, guidelines and resources for non-government organisations that are planning to implement shared or collaborative arrangements with other agencies. It summarises results from an evaluation of the implementation phase of the Multi-Tenant Service Centre (MTSC) Pilots Project, which was completed in June 2008. This evaluation shows that developing and implementing shared and collaborative arrangements is a complex process that presents many risks, challenges and barriers to success, but can have many potential benefits for non government organisations. As this report makes clear, there is no ‘one size fits all’ approach to this process. The MTSC Pilots Project was conducted by the Department of Communities (DoC), Queensland Government, as part of its Strengthening Non-Government Organisations strategy. The objective of the MTSC Pilots initiative was to co-locate separate service providers in an appropriately located centre, operating with effective and transparent management, which enabled service providers to improve client services. Three MTSC consortiums in Mackay, Caboolture and Toowoomba were selected as the pilots over a four year period from 2006 – 2010.

Power law distributions in entrepreneurship : implications for theory and research

A long-held assumption in entrepreneurship research is that normal (i.e., Gaussian) distributions characterize variables of interest for both theory and practice. We challenge this assumption by examining more than 12,000 nascent, young, and hyper-growth firms. Results reveal that variables which play central roles in resource-, cognition-, action-, and environment-based entrepreneurship theories exhibit highly skewed power law distributions, where a few outliers account for a disproportionate amount of the distribution's total output. Our results call for the development of new theory to explain and predict the mechanisms that generate these distributions and the outliers therein. We offer a research agenda, including a description of non-traditional methodological approaches, to answer this call.

Process engineering aspects of plasmid-based biopharmaceuticals production : tackling the threatening vaccine shortages to prevent global pandemics

Infectious diseases such as SARS, influenza and bird flu have the potential to cause global pandemics; a key intervention will be vaccination. Hence, it is imperative to have in place the capacity to create vaccines against new diseases in the shortest time possible. In 2004, The Institute of Medicine asserted that the world is tottering on the verge of a colossal influenza outbreak. The institute stated that, inadequate production system for influenza vaccines is a major obstruction in the preparation towards influenza outbreaks. Because of production issues, the vaccine industry is facing financial and technological bottlenecks: In October 2004, the FDA was caught off guard by the shortage of flu vaccine, caused by a contamination in a US-based plant (Chiron Corporation), one of the only two suppliers of US flu vaccine. Due to difficulties in production and long processing times, the bulk of the world's vaccine production comes from very small number of companies compared to the number of companies producing drugs. Conventional vaccines are made of attenuated or modified forms of viruses. Relatively high and continuous doses are administered when a non-viable vaccine is used and the overall protective immunity obtained is ephemeral. The safety concerns of viral vaccines have propelled interest in creating a viable replacement that would be more effective and safer to use.

Non-market use and non-use values for preserving ecosystem services over time : a choice experiment application to coral reef ecosystems in New Caledonia

Non-use values (i.e. economic values assigned by individuals to ecosystem goods and services unrelated to current or future uses) provide one of the most compelling incentives for the preservation of ecosystems and biodiversity. Assessing the non-use values of non-users is relatively straightforward using stated preference methods, but the standard approaches for estimating non-use values of users (stated decomposition) have substantial shortcomings which undermine the robustness of their results. In this paper, we propose a pragmatic interpretation of non-use values to derive estimates that capture their main dimensions, based on the identification of a willingness to pay for ecosystem protection beyond one's expected life. We empirically test our approach using a choice experiment conducted on coral reef ecosystem protection in two coastal areas in New Caledonia with different institutional, cultural, environmental and socio-economic contexts. We compute individual willingness to pay estimates, and derive individual non-use value estimates using our interpretation. We find that, a minima, estimates of non-use values may comprise between 25 and 40% of the mean willingness to pay for ecosystem preservation, less than has been found in most studies.

The role of non-thermal plasma technique in {NOx} treatment: A review

Non-thermal plasma (NTP) has been introduced over the past several years as a promising method for nitrogen oxide (NOx) removal. The intent, when using NTP, is to selectively transfer input electrical energy to the electrons, and to not expend this in heating the entire gas stream, which generates free radicals through collisions, and promotes the desired chemical changes in the exhaust gases. The generated active species react with the pollutant molecules and decompose them. This paper reviews and summarizes relevant literature regarding various aspects of the application of {NTP} technology on {NOx} removal from exhaust gases. A comprehensive description of available scientific literature on {NOx} removal using {NTP} technology is presented, including various types of NTP, e.g. dielectric barrier discharge, corona discharge and electron beam. Furthermore, the combination of {NTP} with catalyst and adsorbent for better {NOx} removal efficiency is presented in detail. The removal of {NOx} from both simulated gases and real diesel engines is also considered in this review paper. As {NTP} is a new technique and is not yet commercialized, there is a need for more studies to be performed in this field.

Log delta analysis: Interpretable differencing of Business process event logs

This paper addresses the problem of identifying and explaining behavioral differences between two business process event logs. The paper presents a method that, given two event logs, returns a set of statements in natural language capturing behavior that is present or frequent in one log, while absent or infrequent in the other. This log delta analysis method allows users to diagnose differences between normal and deviant executions of a process or between two versions or variants of a process. The method relies on a novel approach to losslessly encode an event log as an event structure, combined with a frequency-enhanced technique for differencing pairs of event structures. A validation of the proposed method shows that it accurately diagnoses typical change patterns and can explain differences between normal and deviant cases in a real-life log, more compactly and precisely than previously proposed methods.

BPMN Miner: Automated Discovery of BPMN Process Models with Hierarchical Structure

Existing techniques for automated discovery of process models from event logs gen- erally produce flat process models. Thus, they fail to exploit the notion of subprocess as well as error handling and repetition constructs provided by contemporary process modeling notations, such as the Business Process Model and Notation (BPMN). This paper presents a technique for automated discovery of hierarchical BPMN models con- taining interrupting and non-interrupting boundary events and activity markers. The technique employs functional and inclusion dependency discovery techniques in order to elicit a process-subprocess hierarchy from the event log. Given this hierarchy and the projected logs associated to each node in the hierarchy, parent process and subprocess models are then discovered using existing techniques for flat process model discovery. Finally, the resulting models and logs are heuristically analyzed in order to identify boundary events and markers. By employing approximate dependency discovery tech- niques, it is possible to filter out noise in the event log arising for example from data entry errors or missing events. A validation with one synthetic and two real-life logs shows that process models derived by the proposed technique are more accurate and less complex than those derived with flat process discovery techniques. Meanwhile, a validation on a family of synthetically generated logs shows that the technique is resilient to varying levels of noise.

Peripapillary choroidal thickness in childhood

Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p<0.001) and sector position (p<0.001) in this population of children. The innermost annulus (closest to the edge of the optic disc) exhibited the thinnest choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p<0.001). RNFL thickness also varied significantly with annulus location and sector (p<0.001), and showed differences in thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle from the optic nerve head boundary. A significant thinning of the peripapillary choroid associated with myopia in childhood was also observed in both nasal and temporal regions. The changes in peripapillary RNFL and choroidal thickness associated with refractive error are consistent with a redistribution of these tissues occurring with myopic axial elongation in childhood.

Performance evaluation of non-thermal plasma on particulate matter, ozone and CO2 correlation for diesel exhaust emission reduction

This study is seeking to investigate the effect of non-thermal plasma technology in the abatement of particulate matter (PM) from the actual diesel exhaust. Ozone (O3) strongly promotes PM oxidation, the main product of which is carbon dioxide (CO2). PM oxidation into the less harmful product (CO2) is the main objective whiles the correlation between PM, O3 and CO2 is considered. A dielectric barrier discharge reactor has been designed with pulsed power technology to produce plasma inside the diesel exhaust. To characterise the system under varied conditions, a range of applied voltages from 11 kVPP to 21kVPP at repetition rates of 2.5, 5, 7.5 and 10 kHz, have been experimentally investigated. The results show that by increasing the applied voltage and repetition rate, higher discharge power and CO2 dissociation can be achieved. The PM removal efficiency of more than 50% has been achieved during the experiments and high concentrations of ozone on the order of a few hundreds of ppm have been observed at high discharge powers. Furthermore, O3, CO2 and PM concentrations at different plasma states have been analysed for time dependence. Based on this analysis, an inverse relationship between ozone concentration and PM removal has been found and the role of ozone in PM removal in plasma treatment of diesel exhaust has been highlighted.