A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells

In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

Multi-step ahead direct prediction for the machine condition prognosis using regression trees and neuro-fuzzy systems

This paper presents an approach to predict the operating conditions of machine based on classification and regression trees (CART) and adaptive neuro-fuzzy inference system (ANFIS) in association with direct prediction strategy for multi-step ahead prediction of time series techniques. In this study, the number of available observations and the number of predicted steps are initially determined by using false nearest neighbor method and auto mutual information technique, respectively. These values are subsequently utilized as inputs for prediction models to forecast the future values of the machines’ operating conditions. The performance of the proposed approach is then evaluated by using real trending data of low methane compressor. A comparative study of the predicted results obtained from CART and ANFIS models is also carried out to appraise the prediction capability of these models. The results show that the ANFIS prediction model can track the change in machine conditions and has the potential for using as a tool to machine fault prognosis.

Plantar fasciitis : are pain and fascial thickness associated with arch shape and loading?

Background and Purpose Although plantar fascial thickening is a sonographic criterion for the diagnosis of plantar fasciitis, the effect of local loading and structural factors on fascial morphology are unknown. The purposes of this study were to compare sonographic measures of fascial thickness and radiographic measures of arch shape and regional loading of the foot during gait in individuals with and without unilateral plantar fasciitis and to investigate potential relationships between these loading and structural factors and the morphology of the plantar fascia in individuals with and without heel pain. Subjects The participants were 10 subjects with unilateral plantar fasciitis and 10 matched asymptomatic controls. Methods Heel pain on weight bearing was measured by a visual analog scale. Fascial thickness and static arch angle were determined from bilateral sagittal sonograms and weight-bearing lateral foot roentgenograms. Regional plantar loading was estimated from a pressure plate. Results On average, the plantar fascia of the symptomatic limb was thicker than the plantar fascia of the asymptomatic limb (6.1±1.4 mm versus 4.2±0.5 mm), which, in turn, was thicker than the fascia of the matched control limbs (3.4±0.5 mm and 3.5±0.6 mm). Pain was correlated with fascial thickness, arch angle, and midfoot loading in the symptomatic foot. Fascial thickness, in turn, was positively correlated with arch angle in symptomatic and asymptomatic feet and with peak regional loading of the midfoot in the symptomatic limb. Discussion and Conclusion The findings indicate that fascial thickness and pain in plantar fasciitis are associated with the regional loading and static shape of the arch.

The contribution of maize cropping in the Midwest USA to global warming: A regional estimate

Agricultural soils emit about 50% of the global flux of N2O attributable to human influence, mostly in response to nitrogen fertilizer use. Recent evidence that the relationship between N2O fluxes and N-fertilizer additions to cereal maize are non-linear provides an opportunity to estimate regional N2O fluxes based on estimates of N application rates rather than as a simple percentage of N inputs as used by the Intergovernmental Panel on Climate Change (IPCC). We combined a simple empirical model of N2O production with the SOCRATES soil carbon dynamics model to estimate N2O and other sources of Global Warming Potential (GWP) from cereal maize across 19,000 cropland polygons in the North Central Region (NCR) of the US over the period 1964–2005. Results indicate that the loading of greenhouse gases to the atmosphere from cereal maize production in the NCR was 1.7 Gt CO2e, with an average 268 t CO2e produced per tonne of grain. From 1970 until 2005, GHG emissions per unit product declined on average by 2.8 t CO2e ha−1 annum−1, coinciding with a stabilisation in N application rate and consistent increases in grain yield from the mid-1970’s. Nitrous oxide production from N fertilizer inputs represented 59% of these emissions, soil C decline (0–30 cm) represented 11% of total emissions, with the remaining 30% (517 Mt) from the combustion of fuel associated with farm operations. Of the 126 Mt of N fertilizer applied to cereal maize from 1964 to 2005, we estimate that 2.2 Mt N was emitted as N2O when using a non-linear response model, equivalent to 1.75% of the applied N.

Towards automated and in-situ, near-real time 3-D reconstruction of coral reef environments

Coral reefs are biologically complex ecosystems that support a wide variety of marine organisms. These are fragile communities under enormous threat from natural and human-based influences. Properly assessing and measuring the growth and health of reefs is essential to understanding impacts of ocean acidification, coastal urbanisation and global warming. In this paper, we present an innovative 3-D reconstruction technique based on visual imagery as a non-intrusive, repeatable, in situ method for estimating physical parameters, such as surface area and volume for efficient assessment of long-term variability. The reconstruction algorithms are presented, and benchmarked using an existing data set. We validate the technique underwater, utilising a commercial-off-the-shelf camera and a piece of staghorn coral, Acropora cervicornis. The resulting reconstruction is compared with a laser scan of the coral piece for assessment and validation. The comparison shows that 77% of the pixels in the reconstruction are within 0.3 mm of the ground truth laser scan. Reconstruction results from an unknown video camera are also presented as a segue to future applications of this research.

High-density lipoprotein and the risk of recurrent venous thromboembolism

BACKGROUND - High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism. METHODS AND RESULTS - We studied 772 patients after a first spontaneous venous thromboembolism (average follow-up 48 months) and recorded the end point of symptomatic recurrent venous thromboembolism, which developed in 100 of the 772 patients. The relationship between plasma lipoprotein parameters and recurrence was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Compared with those without recurrence, patients with recurrence had lower mean (±SD) levels of apolipoprotein AI (1.12±0.22 versus 1.23±0.27 mg/mL, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/mL in plasma apolipoprotein AI. Compared with patients with apolipoprotein AI levels in the lowest tertile (<1.07 mg/mL), the relative risk of recurrence was 0.46 (95% CI, 0.27 to 0.77) for the highest-tertile patients (apolipoprotein AI >1.30 mg/mL) and 0.78 (95% CI, 0.50 to 1.22) for midtertile patients (apolipoprotein AI of 1.07 to 1.30 mg/mL). Using nuclear magnetic resonance, we determined the levels of 10 major lipoprotein subclasses and HDL cholesterol for 71 patients with recurrence and 142 matched patients without recurrence. We found a strong trend for association between recurrence and low levels of HDL particles and HDL cholesterol. CONCLUSIONS - Patients with high levels of apolipoprotein AI and HDL have a decreased risk of recurrent venous thromboembolism. © 2007 American Heart Association, Inc.

Accommodating serendipity in the active studio

This paper presents a series of ongoing experiments to facilitate serendipity in the design studio through a diversity of delivery modes. These experiments are conducted in a second year architectural design studio, and include physical, dramatic and musical performance. The act of designing is always exploratory, always seeking an unknown resolution, and the ability to see and capture the value in the unexpected is a critical aspect of such creative design practice. Engaging with the unexpected is however a difficult ability to develop in students. Just how can a student be schooled in such abilities when the challenge and the context are unforeseeable? How can students be offered meaningful feedback about an issue that cannot be predicted, when feedback comes in the form of extrinsic assessment from a tutor? This project establishes a number of student activities that seek to provide intrinsic feedback from the activity itself. Further to this, the project seeks to heighten student engagement with the project through physical expression and performance: utilising more of the students’ senses than just vision and hearing. Diana Laurillard’s theories of conversational frameworks (2002) are used to interrogate the act of dramatic performance as an act of learning, with particular reference to the serendipitous activities of design. Such interrogation highlights the feedback mechanisms that facilitate intrinsic feedback and fast, if not instantaneous, cycles of learning. The physical act of performance itself provides a learning experience that is not replicable in other modes of delivery. Student feedback data and independent assessment of project outcomes are used to assess the success of this studio model.

Active buildings : what can we do about buildings that simply stand still?

This paper presents background of our research and result of our pilot study to find methods for convincing building users to become active building participants. We speculate this is possible by allowing and motivating users to customise and manage their own built environments. The ultimate aim of this research is to develop open, flexible and adaptive systems that bring awareness to building users to the extent they recognise spaces are for them to change rather than accept spaces are fixed and they are the ones to adapt. We argue this is possible if the architectural hardware is designed to adapt to begin with and more importantly if there are appropriate user interfaces that are designed to work with the hardware. A series of simple prototypes were made to study possibilities through making, installing and experiencing them. Ideas discussed during making and experiencing of prototypes were evaluated to generate further ideas. This method was very useful to speculate unexplored and unknown issues with respect to developing user interfaces for active buildings.

Shouting from the rooftops : Queer digital storytelling for social impact

This chapter explores some of the practical and theoretical obstacles and opportunities for self-expression experienced by a group of Queer Dig- ital Storytellers who primarily make and distribute their stories online. “Queer” in this chapter encompasses a diverse range of gender and sexual identities and perspectives on same, including the heterosexual children of queer parents and heterosexual parents of queer children. As such it is also used as a unifying moniker by participants in the Rainbow Family Tree case study that is examined in this chapter. The Digital Storytellers in this case study are largely motivated by a desire to have an impact on social attitudes towards gender and sexuality, both in their personal province of friends and family, and in public domains constituted of unknown or invisible audiences. The privacy and publicity dilemmas that will be considered arise out of positioning personal stories in the public domain and the quandaries that emerge from an activist desire to speak truth to power that is located across a wide cross section of audiences.

Fault diagnostics and supervised testing : How fault diagnostic tools can be proactive?

The topic of fault detection and diagnostics (FDD) is studied from the perspective of proactive testing. Unlike most research focus in the diagnosis area in which system outputs are analyzed for diagnosis purposes, in this paper the focus is on the other side of the problem: manipulating system inputs for better diagnosis reasoning. In other words, the question of how diagnostic mechanisms can direct system inputs for better diagnosis analysis is addressed here. It is shown how the problem can be formulated as decision making problem coupled with a Bayesian Network based diagnostic mechanism. The developed mechanism is applied to the problem of supervised testing in HVAC systems.

Parent decisions regarding paid work and care of the child

Australia has witnessed a continual increase in maternal employment over the past two decades, which has placed focus on child care- its effects on the child and on early childhood education and care policy and provision. The engagement of women in the paid workforce contributes to national economic development, and is recognised in government policy incentives such as cash subsidies and tax relief for child care fees. These incentives are targeted towards mothers, to encourage them to engage in paid work. Making a contribution to the family’s economy and to a mother’s economic self sufficiency are two key drivers for women’s engagement in satisfying paid work. Many women also seek to maintain a personal investment in the development of their career, simultaneously ensuring that the child is experiencing suitable care. Policies that support women’s choices for satisfying workforce engagement and care arrangements are prudent for ensuring productivity of the economy as well as for enhancing the wellbeing of parents and children (OECD, 2007). Policies that provide family friendly employment arrangements, paid parental leave, and child care support, directly affect maternal employment decisions. Availability of family friendly employment policies is viewed as one way to not only promote gender equity in employment opportunities but also support the wellbeing of children and families (OECD, 2007). Yet there are not comprehensive and coherent policies on work and family in Australia. Australia is due to implement its first paid parental leave scheme in January, 2011. At the time of the data collection of this research, June 2007 to December 2008, Australia had no statutory provision for paid parental leave. To date, most research has focused on the consequences of paid work and care decisions made by women. Far less is known about the processes of decision-making and reasons underlying women’s choices. Investigation of what is most salient for women as they make decisions regarding engagement in paid work, and care for their child is important in order to inform policy and practices related to parental leave, family friendly employment and care for the child. This prospective longitudinal research was of 124 Australian expectant first-time mothers who completed questionnaires in their third trimester of pregnancy, and again at six and twelve months postpartum. First-time expectant mothers' decisions regarding engaging in paid work and selecting care for their child represent those of a group who are invested in motherhood and have usually had direct experience of engaging in paid work. They therefore provide an important insight into society’s idealised views about motherhood and the emotional and social uncertainty of making personal decisions where the consequences of such decisions are unknown. These decisions reflect public beliefs about the role of women in contributing to the country’s productivity and decisions about providing for the economic and emotional care needs of their family. As so little is known about the reasoning and processes of decision-making of women’s choices regarding paid work and care of the child this research was designed to capture expectant first-time mother’s preferred options for engaging in paid work and the care of their child, and investigate their actual decisions made at six and 12 months postpartum. To capture preferred options, decisions and outcomes of decisions regarding paid work and care of the child a prospective longitudinal research design was utilised. This design had three important components that addressed key limitations in the extant literature. First the research commenced in pregnancy in order to investigate preferences and beliefs about paid work and care and to examine baseline data that may influence decisions made as the women returned to paid work. Second the research involved longitudinal tracking from the antenatal time point to six and 12 months postpartum in order to identify the influences on decisions made. Third the research measured outcomes of the decisions made at each time point. This research examined the intentions, preferences, beliefs, influences, and outcomes of the decisions about engagement in paid work and choice of care. The analyses examined factors predicting return to paid work, the timing of return and extent of engagement in paid work; the care for the child; satisfaction with paid work; satisfaction with care for the child, motherhood and fulfilment; and maternal wellbeing at six and 12 months postpartum. The factors of interest were both rational/economic (availability and extent of paid and unpaid maternity leave; flexible work patterns) and emotional/affective (career satisfaction, investment in motherhood, and concern with quality of care for the child). Results indicated a group preference, and realisation for, return to paid work within the first year after the birth of a child but with reduction in hours to part-time. Most women saw paid work not only as a source of income but also as source of personal satisfaction. There were four key themes arising from this research. First, the women strived to feel emotionally secure when deciding about engaging in paid work and care of the child. To achieve emotional security women made their decisions for paid work and care of the child differently. A woman’s decision for maternal employment is a function of her personal beliefs, preferences and context regarding paid work and care of the child. She adjusts her established work identity with her new identity as a mother. The second key theme from this research is that the women made their decisions for maternal employment in response to their personal context and there were different levels of opportunities between the women’s choices. There is inequity of entitlement regarding work conditions associated with a woman’s education level. This has implications for the woman’s engagement in paid work, and her child’s health and wellbeing. The third key theme is that the quality of the child’s care mattered to the women in the research. They preferred care provided by parents and/or relatives more than any other types of care. The fourth key theme identified that satisfaction and wellbeing outcomes experienced as a result of maternal employment decisions were a complex interaction between multiple factors that change across time with the ongoing development of the mother’s identity, and the development of the child. The implications for policy within Australia are that the employment of mothers in the workforce necessitates that non-parental care becomes a public concern, where there is universal access to good quality affordable care for every child, not just for those who can afford it. This is equitable and represents real choice while supporting the rights of the child (Thorpe, Cloney & Tayler, 2010), protecting and promoting the public interest (Cleveland & Krashinsky, 2010). Children’s health and wellbeing will be supported (Moore & Oberklaid, 2010) while children are in non-parental care, and they will be exposed to environments and experiences that support their learning and development. The significant design of the research enabled the trajectories of first-time expectant women to be tracked from the antenatal point to 12 months postpartum. But there were limitations: the small sample size, the over-representation of the sample being highly educated and the nature of a longitudinal research that is set within the economic, social and political context at that time. These limitations are discussed in relation to suggestions for future research.

Turbulent velocity and suspended sediment concentration measurements in an urban environment of the Brisbane River Flood Plain at Gardens Point on 12-13 January 2011

The flood flow in urbanised areas constitutes a major hazard to the population and infrastructure as seen during the summer 2010-2011 floods in Queensland (Australia). Flood flows in urban environments have been studied relatively recently, although no study considered the impact of turbulence in the flow. During the 12-13 January 2011 flood of the Brisbane River, some turbulence measurements were conducted in an inundated urban environment in Gardens Point Road next to Brisbane's central business district (CBD) at relatively high frequency (50 Hz). The properties of the sediment flood deposits were characterised and the acoustic Doppler velocimeter unit was calibrated to obtain both instantaneous velocity components and suspended sediment concentration in the same sampling volume with the same temporal resolution. While the flow motion in Gardens Point Road was subcritical, the water elevations and velocities fluctuated with a distinctive period between 50 and 80 s. The low frequency fluctuations were linked with some local topographic effects: i.e, some local choke induced by an upstream constriction between stairwells caused some slow oscillations with a period close to the natural sloshing period of the car park. The instantaneous velocity data were analysed using a triple decomposition, and the same triple decomposition was applied to the water depth, velocity flux, suspended sediment concentration and suspended sediment flux data. The velocity fluctuation data showed a large energy component in the slow fluctuation range. For the first two tests at z = 0.35 m, the turbulence data suggested some isotropy. At z = 0.083 m, on the other hand, the findings indicated some flow anisotropy. The suspended sediment concentration (SSC) data presented a general trend with increasing SSC for decreasing water depth. During a test (T4), some long -period oscillations were observed with a period about 18 minutes. The cause of these oscillations remains unknown to the authors. The last test (T5) took place in very shallow waters and high suspended sediment concentrations. It is suggested that the flow in the car park was disconnected from the main channel. Overall the flow conditions at the sampling sites corresponded to a specific momentum between 0.2 to 0.4 m2 which would be near the upper end of the scale for safe evacuation of individuals in flooded areas. But the authors do not believe the evacuation of individuals in Gardens Point Road would have been safe because of the intense water surges and flow turbulence. More generally any criterion for safe evacuation solely based upon the flow velocity, water depth or specific momentum cannot account for the hazards caused by the flow turbulence, water depth fluctuations and water surges.

Application of electrical resistivity method to detect deep cracks in unsaturated residual soil slope

Crack is a significant influential factor in soil slope that could leads to rainfall-induced slope instability. Existence of cracks at soil surface will decrease the shear strength and increase the hydraulic conductivity of soil slope. Although previous research has shown the effect of surface-cracks in soil stability, the influence of deep-cracks on soil stability is still unknown. The limited availability of deep crack data due to the difficulty of effective investigate methods could be one of the obstacles. Current technology in electrical resistivity can be used to detect deep-cracks in soil. This paper discusses deep cracks in unsaturated residual soil slopes in Indonesia using electrical resistivity method. The field investigation such as bore hole and SPT tests was carried out at multiple locations in the area where the electrical resistivity testing have been conducted. Subsequently, the results from bore-hole and SPT test were used to verify the results of the electrical resistivity test. This study demonstrates the benefits and limitations of the electrical resistivity in detecting deep-cracks in a residual soil slopes.

The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol

Abstract Background: The current obesity epidemic is thought to be partly driven by over-consumption of sugar-sweetened diets and soft drinks. Loss-of-control over eating and addiction to drugs of abuse share overlapping brain mechanisms including changes in motivational drive, such that stimuli that are often no longer ‘liked’ are still intensely ‘wanted’ [7,8]. The neurokinin 1 (NK1) receptor system has been implicated in both learned appetitive behaviors and addiction to alcohol and opioids; however, its role in natural reward seeking remains unknown. Methodology/Principal Findings: We sought to determine whether the NK1-receptor system plays a role in the reinforcing properties of sucrose using a novel selective and clinically safe NK1-receptor antagonist, ezlopitant (CJ-11,974), in three animal models of sucrose consumption and seeking. Furthermore, we compared the effect of ezlopitant on ethanol consumption and seeking in rodents. The NK1-receptor antagonist, ezlopitant decreased appetitive responding for sucrose more potently than for ethanol using an operant self-administration protocol without affecting general locomotor activity. To further evaluate the selectivity of the NK1-receptor antagonist in decreasing consumption of sweetened solutions, we compared the effects of ezlopitant on water, saccharin-, and sodium chloride (NaCl) solution consumption. Ezlopitant decreased intake of saccharin but had no effect on water or salty solution consumption. Conclusions/Significance: The present study indicates that the NK1-receptor may be a part of a common pathway regulating the self-administration, motivational and reinforcing aspects of sweetened solutions, regardless of caloric value, and those of substances of abuse. Additionally, these results indicate that the NK1-receptor system may serve as a therapeutic target for obesity induced by over-consumption of natural reinforcers.

Measuring and decomposing changes in agricultural productivity, nitrogen use efficiency and cumulative exergy efficiency: Application to OECD agriculture

This paper uses an aggregate quantity space to decompose the temporal changes in nitrogen use efficiency and cumulative exergy use efficiency into changes of Moorsteen–Bjurek (MB) Total Factor Productivity (TFP) changes and changes in the aggregate nitrogen and cumulative exergy contents. Changes in productivity can be broken into technical change and changes in various efficiency measures such as technical efficiency, scale efficiency and residual mix efficiency. Changes in the aggregate nitrogen and cumulative exergy contents can be driven by changes in the quality of inputs and outputs and changes in the mixes of inputs and outputs. Also with cumulative exergy content analysis, changes in the efficiency in input production can increase or decrease the cumulative exergy transformity of agricultural production. The empirical study in 30 member countries of the Organisation for Economic Co-operation Development from 1990 to 2003 yielded some important findings. The production technology progressed but there were reductions in technical efficiency, scale efficiency and residual mix efficiency levels. This result suggests that the production frontier had shifted up but there existed lags in the responses of member countries to the technological change. Given TFP growth, improvements in nutrient use efficiency and cumulative exergy use efficiency were counteracted by reductions in the changes of the aggregate nitrogen contents ratio and aggregate cumulative exergy contents ratio. The empirical results also confirmed that different combinations of inputs and outputs as well as the quality of inputs and outputs could have more influence on the growth of nutrient and cumulative exergy use efficiency than factors that had driven productivity change. Keywords: Nutrient use efficiency; Cumulative exergy use efficiency; Thermodynamic efficiency change; Productivity growth; OECD agriculture; Sustainability