Efficient computation of causal behavioural profiles using structural decomposition

Identification of behavioural contradictions is an important aspect of software engineering, in particular for checking the consistency between a business process model used as system specification and a corresponding workflow model used as implementation. In this paper, we propose causal behavioural profiles as the basis for a consistency notion, which capture essential behavioural information, such as order, exclusiveness, and causality between pairs of activities. Existing notions of behavioural equivalence, such as bisimulation and trace equivalence, might also be applied as consistency notions. Still, they are exponential in computation. Our novel concept of causal behavioural profiles provides a weaker behavioural consistency notion that can be computed efficiently using structural decomposition techniques for sound free-choice workflow systems if unstructured net fragments are acyclic or can be traced back to S- or T-nets.

A brief guide to synchrotron radiation-based microtomography in (structural) geology and rock mechanics

This contribution outlines Synchrotron-based X-ray micro-tomography and its potential use in structural geology and rock mechanics. The paper complements several recent reviews of X-ray microtomography. We summarize the general approach to data acquisition, post-processing as well as analysis and thereby aim to provide an entry point for the interested reader. The paper includes tables listing relevant beamlines, a list of all available imaging techniques, and available free and commercial software packages for data visualization and quantification. We highlight potential applications in a review of relevant literature including time-resolved experiments and digital rock physics. The paper concludes with a report on ongoing developments and upgrades at synchrotron facilities to frame the future possibilities for imaging sub-second processes in centimetre-sized samples.

Characterization of ENU-induced mutations in red blood cell structural proteins

Murine models with modified gene function as a result of N-ethyl-N-nitrosourea (ENU) mutagenesis have been used to study phenotypes resulting from genetic change. This study investigated genetic factors associated with red blood cell (RBC) physiology and structural integrity that may impact on blood component storage and transfusion outcome. Forward and reverse genetic approaches were employed with pedigrees of ENU-treated mice using a homozygous recessive breeding strategy. In a “forward genetic” approach, pedigree selection was based upon identification of an altered phenotype followed by exome sequencing to identify a causative mutation. In a second strategy, a “reverse genetic” approach based on selection of pedigrees with mutations in genes of interest was utilised and, following breeding to homozygosity, phenotype assessed. Thirty-three pedigrees were screened by the forward genetic approach. One pedigree demonstrated reticulocytosis, microcytic anaemia and thrombocytosis. Exome sequencing revealed a novel single nucleotide variation (SNV) in Ank1 encoding the RBC structural protein ankyrin-1 and the pedigree was designated Ank1EX34. The reticulocytosis and microcytic anaemia observed in the Ank1EX34 pedigree were similar to clinical features of hereditary spherocytosis in humans. For the reverse genetic approach three pedigrees with different point mutations in Spnb1 encoding RBC protein spectrin-1β, and one pedigree with a mutation in Epb4.1, encoding band 4.1 were selected for study. When bred to homozygosity two of the spectrin-1β pedigrees (a, b) demonstrated increased RBC count, haemoglobin (Hb) and haematocrit (HCT). The third Spnb1 mutation (spectrin-1β c) and mutation in Epb4.1 (band 4.1) did not significantly affect the haematological phenotype, despite these two mutations having a PolyPhen score predicting the mutation may be damaging. Exome sequencing allows rapid identification of causative mutations and development of databases of mutations predicted to be disruptive. These tools require further refinement but provide new approaches to the study of genetically defined changes that may impact on blood component storage and transfusion outcome.

Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone

Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Δ4-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Δ4-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Δ4-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Δ4-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.

Performance-based structural fire design and testing of structures

Fire incident in buildings is common in Hong Kong and this could lead to heavy casualties due to its high population density, so the fire safety design of the framed structure is an important research topic. This paper describes a computer tool for determination of capacity of structural safety against various fire scenarios and the well-accepted second-order direct plastic analysis is adopted for simulation of material yielding and buckling. A computer method is developed to predict structural behaviour of bare steel framed structures at elevated temperatures but the work can be applied to structures made of other materials. These effects of thermal expansion and material degradation due to heating are required to be considered in order to capture the actual behavior of the structure under fire. Degradation of material strength with increasing temperature is included by a set of temperature-stress-strain curves according to BS5950 Part 8 mainly, which implicitly allows for creep deformation. Several numerical and experimental verifications of framed structures are presented and compared against solutions by other researchers. The proposed method allows us to adopt the truly performance-based structural fire analysis and design with significant saving in cost and time.

Effect of strong acids on red mud structural and fluoride adsorption properties

The removal of fluoride using red mud has been improved by acidifying red mud with hydrochloric, nitric and sulphuric acid. This investigation shows that the removal of fluoride using red mud is significantly improved if red mud is initially acidified. The acidification of red mud causes sodalite and cancrinite phases to dissociate, confirmed by the release of sodium and aluminium into solution as well as the disappearance of sodalite bands and peaks in infrared and X-ray diffraction data. The dissolution of these mineral phases increases the amount of available iron and aluminium oxide/hydroxide sites that are accessible for the adsorption of fluoride. The removal of fluoride is dependent on the charge of iron and aluminium oxide/hydroxides on the surface of red mud. Acidifying red mud with hydrochloric, nitric and sulphuric acid resulted in surface sites of the form ≡ SOH2+ and ≡ SOH. Optimum removal is obtained when the majority of surface sites are in the form ≡ SOH2+ as the substitution of a fluoride ion doesn’t cause a significant increase in pH. This investigation shows the importance of having a low and consistent pH for the removal of fluoride from aqueous solutions using red mud.

Automatic classification of human epithelial type 2 cell indirect immunofluorescence images using cell pyramid matching

This paper describes a novel system for automatic classification of images obtained from Anti-Nuclear Antibody (ANA) pathology tests on Human Epithelial type 2 (HEp-2) cells using the Indirect Immunofluorescence (IIF) protocol. The IIF protocol on HEp-2 cells has been the hallmark method to identify the presence of ANAs, due to its high sensitivity and the large range of antigens that can be detected. However, it suffers from numerous shortcomings, such as being subjective as well as time and labour intensive. Computer Aided Diagnostic (CAD) systems have been developed to address these problems, which automatically classify a HEp-2 cell image into one of its known patterns (eg. speckled, homogeneous). Most of the existing CAD systems use handpicked features to represent a HEp-2 cell image, which may only work in limited scenarios. We propose a novel automatic cell image classification method termed Cell Pyramid Matching (CPM), which is comprised of regional histograms of visual words coupled with the Multiple Kernel Learning framework. We present a study of several variations of generating histograms and show the efficacy of the system on two publicly available datasets: the ICPR HEp-2 cell classification contest dataset and the SNPHEp-2 dataset.

Parameter estimation of structural commodity price models

Commodity price modeling is normally approached in terms of structural time-series models, in which the different components (states) have a financial interpretation. The parameters of these models can be estimated using maximum likelihood. This approach results in a non-linear parameter estimation problem and thus a key issue is how to obtain reliable initial estimates. In this paper, we focus on the initial parameter estimation problem for the Schwartz-Smith two-factor model commonly used in asset valuation. We propose the use of a two-step method. The first step considers a univariate model based only on the spot price and uses a transfer function model to obtain initial estimates of the fundamental parameters. The second step uses the estimates obtained in the first step to initialize a re-parameterized state-space-innovations based estimator, which includes information related to future prices. The second step refines the estimates obtained in the first step and also gives estimates of the remaining parameters in the model. This paper is part tutorial in nature and gives an introduction to aspects of commodity price modeling and the associated parameter estimation problem.

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis

As microenvironmental factors such as three-dimensionality and cell–matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk.

Structural identification of hindered amine light stabilisers in coil coatings using electrospray ionisation tandem mass spectrometry

Hindered amine light stabilisers (HALS) are the most effective antioxidants currently available for polymer systems in post-production, in-service applications, yet the mechanism of their action is still not fully understood. Structural characterisation of HALS in polymer matrices, particularly the identification of structural modifications brought about by oxidative conditions, is critical to aid mechanistic understanding of the prophylactic effects of these molecules. In this work, electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was applied to the analysis of a suite of commercially available 2,2,6,6-tetramethylpiperidine-based HALS. Fragmentation mechanisms for the \[M + H](+) ions are proposed, which provide a rationale for the product ions observed in the MS/MS and MS(3) mass spectra of N-H, N-CH(3), N-C(O)CH(3) and N-OR containing HALS (where R is an alkyl substituent). A common product ion at m/z 123 was identified for the group of antioxidants containing N-H, N-CH3 or N-C(0)CH3 functionality, and this product ion was employed in precursor ion scans on a triple quadrupole mass spectrometer to identify the HALS species present in a crude extract from of a polyester-based coil coating. Using MS/MS, two degradation products were unambiguously identified. This technique provides a simple and selective approach to monitoring HALS structures within complex matrices. Copyright (C) 2010 John Wiley & Sons, Ltd.

Identification of double bond position in lipids : From GC to OzID

Recent developments in mass spectrometry and chromatography provide new possibilities for the identification and in some instances quantification of a wide range of lipids in complex matrices. These advances in analytical technologies have provided a tantalizing glimpse of the true structural diversity of lipids in nature and have reinvigorated interest in the role of lipids in biology. While technological advances have been impressive, difficulties in the ready identification of sites of unsaturation (i.e., double bond position) within these molecules presents a significant impediment to understanding lipid biochemistry. This is of particular importance given the growing body of literature suggesting that the presence of naturally occurring lipid double bond isomers can have a significant influence, both positive and negative, on the development of pathologies such as cancer, cardiovascular disease and type 2 diabetes. This article provides a critical review of the Current suite of analytical approaches to the challenge of identification of the position of carbon-carbon double bonds in intact lipids. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Intrinsics and dynamics of fat grafts : an in vitro study

Background Despite a revived interest in fat grafting procedures, clinicians still fail to demonstrate clearly the in vivo behavior of fat grafts as a dynamic tissue substitute. However, the basic principles in cellular biology teach us that cells can survive and develop, provided that a structural matrix exists that directs their behavior. The purpose of this in vitro study was to analyze that behavior of crude fat grafts, cultured on a three-dimensional laminin-rich matrix. Methods Nonprocessed, human fat biopsy specimens (approximately 1 mm) were inoculated on Matrigel-coated wells to which culture medium was added. The control group consisted of fat biopsy specimens embedded in medium alone. The cellular proliferation pattern was followed over 6 weeks. Additional cultures of primary generated cellular spheroids were performed and eventually subjected to adipogenic differentiation media. Results A progressive outgrowth of fibroblast-like cells from the core fat biopsy specimen was observed in both groups. Within the Matrigel group, an interconnecting three-dimensional network of spindle-shaped cells was established. This new cell colony reproduced spheroids that functioned again as solitary sources of cellular proliferation. Addition of differentiation media resulted in lipid droplet deposition in the majority of generated cells, indicating the initial steps of adipogenic differentiation. Conclusions The authors noticed that crude, nonprocessed fat biopsy specimens do have considerable potential for future tissue engineering-based applications, provided that the basic principles of developmental, cellular biology are respected. Spontaneous in vitro expansion of the stromal cells present in fat grafts within autologous and injectable matrices could create "off-the-shelf" therapies for reconstructive procedures.

Predicting emotional exhaustion among haemodialysis nurses : a structural equation model using Kanter’s structural empowerment theory

Aim To test an explanatory model of the relationships between the nursing work environment, job satisfaction, job stress and emotional exhaustion for haemodialysis nurses, drawing on Kanter's theory of organizational empowerment. Background Understanding the organizational predictors of burnout (emotional exhaustion) in haemodialysis nurses is critical for staff retention and improving nurse and patient outcomes. Previous research has demonstrated high levels of emotional exhaustion among haemodialysis nurses, yet the relationships between nurses' work environment, job satisfaction, stress and emotional exhaustion in this population are poorly understood. Design A cross-sectional online survey. Methods 417 nurses working in haemodialysis units completed an online survey between October 2011–April 2012 using validated measures of the work environment, job satisfaction, job stress and emotional exhaustion. Results Overall, the structural equation model demonstrated adequate fit and we found partial support for the hypothesized relationships. Nurses' work environment had a direct positive effect on job satisfaction, explaining 88% of the variance. Greater job satisfaction, in turn, predicted lower job stress, explaining 82% of the variance. Job satisfaction also had an indirect effect on emotional exhaustion by mitigating job stress. However, job satisfaction did not have a direct effect on emotional exhaustion. Conclusion The work environment of haemodialysis nurses is pivotal to the development of job satisfaction. Nurses' job satisfaction also predicts their level of job stress and emotional exhaustion. Our findings suggest staff retention can be improved by creating empowering work environments that promote job satisfaction among haemodialysis nurses.

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.

The epithelial-mesenchymal transition : new insights in signaling, development, and disease

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a de. ning structural feature of organ development. Current interest in this process, which is described as an epithelial- mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the . rst being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, . brosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and . brosis, as well as the identi. cation of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).