A computer-based simulation of childbirth using the partial Dirichlet–Neumann contact method with total Lagrangian explicit dynamics on the GPU

During physiological or ‘natural’ childbirth, the fetal head follows a distinct motion pattern—often referred to as the cardinal movements or ‘mechanisms’ of childbirth—due to the biomechanical interaction between the fetus and maternal pelvic anatomy. The research presented in this paper introduces a virtual reality-based simulation of physiological childbirth. The underpinning science is based on two numerical algorithms including the total Lagrangian explicit dynamics method to calculate soft tissue deformation and the partial Dirichlet–Neumann contact method to calculate the mechanical contact interaction between the fetal head and maternal pelvic anatomy. The paper describes the underlying mathematics and algorithms of the solution and their combination into a computer-based implementation. The experimental section covers first a number of validation experiments on simple contact mechanical problems which is followed by the main experiment of running a virtual reality childbirth. Realistic mesh models of the fetus, bony pelvis and pelvic floor muscles were subjected to the intra-uterine expulsion forces which aim to propel the virtual fetus through the virtual birth canal. Following a series of simulations, taking variations in the shape and size of the geometric models into account, we consistently observed the cardinal movements in the simulator just as they happen in physiological childbirth. The results confirm the potential of the simulator as a predictive tool for problematic childbirths subject to patient-specific adaptations.

     

Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells

Proteins responsive to androgen and anti-androgen may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. These proteins represent potential diagnostic and therapeutic targets for improved management of prostate cancer. We have investigated the effect of androgen (R1881) and anti-androgen (bicalutamide) on the androgen-responsive prostate cancer LNCaP cell line using a quantitative gel-based proteomic approach. Prior to analysis, the in vitro system was evaluated for reproducibility and validated by appropriate molecular responses to treatment. Six replicate samples were independently generated and analysed by 2-D DIGE. According to strict statistical criteria, 197 spots were differentially expressed, of which we have successfully identified 165 spots corresponding to 125 distinct proteins. Following androgen supplementation, 108 spots (68 proteins) were increased and 57 spots (39 proteins) were decreased. Essentially no difference was observed between control and anti-androgen-treated samples, confirming the absence of "off-target" effects of bicalutamide. Identified proteins were involved in diverse processes including the stress response and intracellular signalling. The potential contribution to disease of these processes and identified constituent proteins are discussed. This rigorous, statistically supported study of androgen responses has provided a number of potential candidates for development as diagnostic/prognostic markers and drug targets.     

Biosynthesis of unusual monocyclic alkenes by the diatom Rhizosolenia setigera (Brightwell)

Novel, polyunsaturated monocyclic sester- and triterpenes isolated from the diatom Rhizosolenia setigera (Brightwell), are biosynthesised mainly via the mevalonate pathway. The experiments involved incubation of the alga with [1-(13)C]acetate, isolation of the alkenes by extraction and silver ion HPLC, followed by determination of the labelling pattern of one of the monocyclic triterpenes by (13)C-NMR spectroscopy. In addition, the extent of (13)C incorporation was also measured by mass spectrometry which revealed that the involvement of the mevalonate route in the biosynthesis of these cyclic compounds was less than for the co-occurring acyclic highly branched isoprenoid alkenes.     

Model selection methodology in supervised learning with evolutionary computation

The expressive power, powerful search capability, and the explicit nature of the resulting models make evolutionary methods very attractive for supervised learning applications in bioinformatics. However, their characteristics also make them highly susceptible to overtraining or to discovering chance relationships in the data. Identification of appropriate criteria for terminating evolution and for selecting an appropriately validated model is vital. Some approaches that are commonly applied to other modelling methods are not necessarily applicable in a straightforward manner to evolutionary methods. An approach to model selection is presented that is not unduly computationally intensive. To illustrate the issues and the technique two bioinformatic datasets are used, one relating to metabolite determination and the other to disease prediction from gene expression data.     

Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling

CD40 function is initiated by tumor necrosis factor (TNF) receptor-associated factor (TRAF) adapter proteins, which play important roles in signaling by numerous receptors. Characterizing roles of individual TRAFs has been hampered by limitations of available experimental models and the poor viability of most TRAF-deficient mice. Here, B cell lines made deficient in TRAF2 using a novel homologous recombination system reveal new roles for TRAF2. We demonstrate that TRAF2 participates in synergy between CD40 and B cell antigen receptor signals, and in CD40-mediated, TNF-dependent IgM production. We also find that TRAF2 participates in the degradation of TRAF3 associated with CD40 signaling, a role that may limit inhibitory actions of TRAF3. Finally, we show that TRAF2 and TRAF6 have overlapping functions in CD40-mediated NF-kappaB activation and CD80 up-regulation. These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms.     

Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa

Recently, we cloned and characterized a full-length cDNA of the hamster Muc1 gene, the expression of which appears to be associated with secretory cell differentiation (Park HR, Hyun SW, and Kim KC. Am J Respir Cell Mol Biol 15: 237-244, 1996). The role of Muc1 mucins in the airway, however, is unknown. In this study, we investigated whether cell surface mucins are adhesion sites for Pseudomonas aeruginosa. Chinese hamster ovary (CHO) cells not normally expressing Muc1 mucin were stably transfected with the hamster Muc1 cDNA, and binding to P. aeruginosa was examined. Our results showed that 1) stably transfected CHO cells expressed both Muc1 mRNA and Muc1 mucins based on Northern and Western blot analyses, 2) Muc1 mucins present on the cell surface were degraded by neutrophil elastase, and 3) expression of Muc1 mucins on the cell surface resulted in a significant increase in adhesion of P. aeruginosa that was completely abolished by either proteolytic cleavage with neutrophil elastase or deletion of the extracellular domain by mutation. We conclude that Muc1 mucins expressed on the surface of CHO cells serve as adhesion sites for P. aeruginosa, suggesting a possible role for these glycoproteins in the early stage of airway infection and providing a model system for studying epithelial cell responses to bacterial adhesion that leads to airway inflammation in general and cystic fibrosis in particular.     

Contact rates of raccoons (Procyon lotor) at a communal feeding site in rural eastern Ontario

Intra- and interspecific contact rates of 12 adult (five females, seven males) raccoons (Procyon lotor) were recorded while these animals fed at a rural garbage dump 40 km north of Kingston, Ontario, Canada from 15 June to 5 September 1995. While raccoons were being observed, they bit, and were bitten, by their conspecifics an average of 0.99 (+/- 0.21) and 1.28 (+/- 0.21) times per hour, respectively, while feeding. Based on mean nightly contact rates (which included time when raccoons were not observed), raccoons bit one of their conspecifics once every 3 nights while feeding. The mean rate of bites made and received per hour for males was not significantly different from lactating females. There was no detectable difference between the mean rate of bites made and received per hour for raccoons which regularly versus occasionally fed at the dump. No interspecific contacts were observed, though raccoons and striped skunks (Mephitis mephitis) often fed at the dump concurrently. The contact rates in this study are the first to be calculated for raccoons directly from field data and will be useful as a point of reference for modeling rabies spread in raccoons in areas with similar site characteristics.