Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Background Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with angiogenesis and poor outcome. TXS has been identified as a potential therapeutic target in NSCLC. This study examines a link between TXS expression, angiogenesis, and survival in NSCLC. Methods TXS and VEGF metabolite levels were measured in NSCLC serum samples (n=46) by EIA. TXB2 levels were correlated with VEGF. A 204-patient TMA was stained for TXS, VEGF, and CD-31 expression. Expression was correlated with a range of clinical parameters, including overall survival. TXS expression was correlated with VEGF and CD-31. Stable TXS clones were generated and the effect of overexpression on tumor growth and angiogenesis markers was examined in-vitro and in-vivo (xenograft mouse model). Results Serum TXB2 levels were correlated with VEGF (p<0.05). TXS and VEGF were expressed to a varying degree in NSCLC tissue. TXS was associated with VEGF (p<0.0001) and microvessel density (CD-31; p<0.05). TXS and VEGF expression levels were higher in adenocarcinoma (p<0.0001) and female patients (p<0.05). Stable overexpression of TXS increased VEGF secretion in-vitro. While no significant association with patient survival was observed for either TXS or VEGF in our patient cohort, TXS overexpression significantly (p<0.05) increased tumor growth in-vivo. TXS overexpression was also associated with higher levels of VEGF, microvessel density, and reduced apoptosis in xenograft tumors. Conclusion TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Towards consonance in urban form

By presenting the past as a repository of the characteristics of urban formation, urban morphology utilizes a knowledge platform as the basis for interpretation of accordant architectural responses (Levy, 1999). Operating within this framework at the scale of architectural features of individual buildings, and imbued with reference to the intrinsic architectural elements of both preceding and existing building forms, micro-morphology (Larkham, 2006, p. 126) provides the efficacy for new architecture that emerges from such a manner of composition...

Bisresorcinols and arbutin derivatives from Grevillea banksii R. Br

This work is part of a series of chemical investigations of the genus Grevillea. Two new arbutin derivatives, seven new bisresorcinols, including a mixture of two isomers, three known flavonol glycosides, and four known resorcinols, including a mixture of two homologous compounds, were isolated from the ethyl acetate extract of the leaves and methanol extract of the stems of Grevillea banksii. The new compounds were identified, on the basis of spectroscopic data, as 6'-O-(3-(2(hydroxymethyl)acryloyloxy)-2-methylpropanoyl)arbutin (1), 6'-O-(2-methylacryloyl)arbutin (2), 5,5'-(4(Z)-dodecen-1,12diyl)bisresorcinol (6), 2'-methyl-5,5'-(4(Z)-tetradecen-1,14-diyl)bisresorcinol (8), 2,2'-di(4-hydroxyprenyl)-5,5'-(6(Z)-tetradecen-1,14-diyl)bisresorcinol (9), 2-(4-acetoxyprenyl)-2'-(4-hydroxyprenyl) 5,5'-(6(Z)-tetradecen-1,14-diyl)bisresorcinol (10), 2-(4-acetoxyprenyl)-2'-(4-hydroxyprenyl)5,5'-(8(Z)-tetradecen-l,14-diyl)bisresorcinol (11), 5,5'-(10(Z)-tetradecen-1-on-diyl)bisresorcinol (12) and 5,5'-(4(Z)-tetradecen-1-on-diyl)bisresorcinol (13).

Bisresorcinol Derivatives from Grevillea glauca

Seven new and three known bisresorcinols, grevirobstol A(=5,5'-((6Z,9Z)-hexadeca-6,9-diene-1,16-diyl)bisresorcinol; 8), 5,5'-[(8Z)-hexadec-8-ene-1,16-diyl]bisresorcinol (9), and 2-methyl-5,5'-[8Z)-hexadec-8-ene-1,16-diyl] bisresorcinol (10) were isolated from the stems of Grevillea glauca. The new compounds were identified on the basis of spectroscopic data as (Z)-6,7-didehydroglaucone A (1), glaucones A and B (2 and 3, resp.), 2-(3-hydroxyisopentyl)bisnorstriatol (4), 2-(3-methylbut-2-en-1-yl)bisnorstriatol (5), 2'-methylgrebustol A (6), and glaucane (7).

Lattice basis delegation in fixed dimension and shorter-ciphertext hierarchical IBE

We present a technique for delegating a short lattice basis that has the advantage of keeping the lattice dimension unchanged upon delegation. Building on this result, we construct two new hierarchical identity-based encryption (HIBE) schemes, with and without random oracles. The resulting systems are very different from earlier lattice-based HIBEs and in some cases result in shorter ciphertexts and private keys. We prove security from classic lattice hardness assumptions.

Tandem B1 SINE retro-elements may provide a basis for natural antisense transcription in the Magi1 locus of the mouse (Mus musculus)

Transposable elements, which are DNA sequences that can move between different sites in genomes, comprise approximately 40% of the genome of mammals and are emerging as important contributors to biological diversity. Here we report a transcription unit lying within intron 1 of the murine Magi1 (membrane associated guanylate kinase inverted 1) gene that codes for a cell-cell junction scaffolding protein. The transcription unit, termed Magi1OS (Magi1 Opposite Strand), originates from a region with tandem B1 short interspersed nuclear elements (SINEs) and is an antisense gene to Magi1. Mag1OS transcription initiates in a proximal B1 element that shows only 4% divergence from the consensus sequence, indicating that it has been recently inserted into the mouse genome and could be replication competent. Moreover, a chimaeric transcript may result from intra-chromosomal interaction and trans-splicing of the Magi1 antisense transcript (Magi1OS) and Ghrl, which codes for the multifunctional peptide hormone ghrelin. These two genes are 20 megabases apart on chromosome 6 and are transcribed in opposite directions. We propose that the Magi1OS locus may serve as a useful model system to study exaptation and retrotransposition of B1 SINEs, as well as to examine the mechanisms of intra-chromosomal trans-splicing.

Soil moisture monitoring at the field scale using neutron probe

Measurement of the moisture variation in soils is required for geotechnical design and research because soil properties and behavior can vary as moisture content changes. The neutron probe, which was developed more than 40 years ago, is commonly used to monitor soil moisture variation in the field. This study reports a full-scale field monitoring of soil moisture using a neutron moisture probe for a period of more than 2 years in the Melbourne (Australia) region. On the basis of soil types available in the Melbourne region, 23 sites were chosen for moisture monitoring down to a depth of 1500 mm. The field calibration method was used to develop correlations relating the volumetric moisture content and neutron counts. Observed results showed that the deepest “wetting front” during the wet season was limited to the top 800 to 1000 mm of soil whilst the top soil layer down to about 550mmresponded almost immediately to the rainfall events. At greater depths (550 to 800mmand below 800 mm), the moisture variations were relatively low and displayed predominantly periodic fluctuations. This periodic nature was captured with Fourier analysis to develop a cyclic moisture model on the basis of an analytical solution of a one-dimensional moisture flow equation for homogeneous soils. It is argued that the model developed can be used to predict the soil moisture variations as applicable to buried structures such as pipes.

The Language : Rationale and Fundamentals

The Business Process Management domain has evolved at a dramatic pace over the past two decades and the notion of the business process has become a ubiquitous part of the modern business enterprise. Most organizations now view their operations in terms of business processes and manage these business processes in the same way as other corporate assets. In recent years, an increasingly broad range of generic technology has become available for automating business processes. This is part of a growing trend in the software engineering field throughout the past 40 years, where aspects of functionality that are potentially reusable on a widespread basis have coalesced into generic software components. Figure 2.1 illustrates this trend and shows how software systems have evolved from the monolithic applications of the 1960s developed in their entirety often by a single development team to today’s offerings that are based on the integration of a range of generic technologies with only a small component of the application actually being developed from scratch. In the 1990s, generic functionality for the automation of business processes first became commercially available in the form of workflow technology and subsequently evolved in the broader field of business process management systems (BPMS). This technology alleviated the necessity to develop process support within applications from scratch and provided a variety of off-the-shelf options on which these requirements could be based. The demand for this technology was significant and it is estimated that by 2000 there were well over 200 distinct workflow offerings in the market, each with a distinct conceptual foundation. Anticipating the difficulties that would be experienced by organizations seeking to utilize and integrate distinct workflow offerings, the Workflow Management Coalition (WfMC), an industry group formed to advance technology in this area, proposed a standard reference model for workflow technology with an express desire to seek a common platform for achieving workflow interoperation.

Methanesulfonic acid-catalyzed conversion of glucose and xylose mixtures to levulinic acid and furfural

Methanesulfonic acid (MSA) was compared with sulfuric acid for the conversion of glucose and xylose mixtures to produce levulinic acid and furfural. The interactions of glucose and xylose, the predominant sugars found in biomass, were found to influence product yields with furfural degradation reactions enhanced under higher reactant loadings. Fast heating rates allowed maximal yields (>60 mol%) of levulinic acid and furfural to be achieved under short reaction times. Under the range of conditions examined, sulfuric acid produced a slight increase in levulinic acid yield by 6% (P = 0.02), although there was no significant difference (P = 0.11) between MSA and sulfuric acid in levulinic acid formed from glucose alone. The amount and type of the solid residue is similar between MSA and sulfuric acid. As such, MSA is a suitable alternative because its use minimizes corrosion and disposal issues associated with mineral acid catalysts. The heating value of the residue was 22 MJ/kg implying that it is a suitable source of fuel. On the basis of these results, a two-stage processing strategy is proposed to target high levulinic acid and furfural yields, and other chemical products (e.g., lactic acid, xylitol, acetic acid and formic acid). This will result in full utilization of bagasse components.

Bayesian P-splines with a multiplicative term in EMG trace data

A method is proposed to describe force or compound muscle action potential (CMAP) trace data collected in an electromyography study for motor unit number estimation (MUNE). Experimental data was collected using incre- mental stimulation at multiple durations. However, stimulus information, vital for alternate MUNE methods, is not comparable for multiple duration data and therefore previous methods of MUNE (Ridall et al., 2006, 2007) cannot be used with any reliability. Hypothesised ring combinations of motor units are mod- elled using a multiplicative factor and Bayesian P-spline formulation. The model describes the process for force and CMAP in a meaningful way.

Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Physiological basis of salt stress tolerance in rice expressing the antiapoptotic gene SfIAP

Programmed cell death-associated genes, especially antiapoptosis-related genes have been reported to confer tolerance to a wide range of biotic and abiotic stresses in dicotyledonous plants such as tobacco (Nicotiana tabacum L.) and tomato (Solanum lycopersicum L.). This is the first time the antiapoptotic gene SfIAP was transformed into a monocotyledonous representative: rice (Oryza sativa L.). Transgenic rice strains expressing SfIAP were generated by the Agrobacterium-mediated transformation method and rice embryogenic calli, and assessed for their ability to confer tolerance to salt stress at both the seedling and reproductive stages using a combination of molecular, agronomical, physiological and biochemical techniques. The results show that plants expressing SfIAP have higher salt tolerance levels in comparison to the wild-type and vector controls. By preventing cell death at the onset of salt stress and maintaining the cell membrane’s integrity, SfIAP transgenic rice plants can retain plant water status, ion homeostasis, photosynthetic efficiency and growth to combat salinity successfully.

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk. © 2013 Springer Science+Business Media New York.

'Look and feel' computer copyright in the United States and Australia (part 1)

United States copyright law -- two streams of computer copyright cases form basis for 'look and feel' litigation, literary work stream and audiovisual work stream -- literary work stream focuses on structure -- audiovisual work steam addresses appearance -- case studies