Computational and Mathematical Modelling of the EGF Receptor System

This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described

Subwavelength anti-diffracting beams propagating over more than 1,000 Rayleigh lengths

Propagating light beams with widths down to and below the optical wavelength require bulky large-aperture lenses and remain focused only for micrometric distances. Here, we report the observation of light beams that violate this localization/depth- of-focus law by shrinking as they propagate, allowing resolution to be maintained and increased over macroscopic propagation lengths. In nanodisordered ferroelectrics we observe a non-paraxial propagation of a sub-micrometre-sized beam for over 1,000 diffraction lengths, the narrowest visible beam reported to date. This unprecedented effect is caused by the nonlinear response of a dipolar glass, which transforms the leading opticalwave equation into a Klein-Gordon-type equation that describes a massive particle field. Our findings open the way to high-resolution optics over large depths of focus, and a route to merging bulk optics into nanodevices

Intracellular Trafficking Considerations in the Development of Natural Ligand-Drug Molecular Conjugates for Cancer

Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular trafficking pathways of the endogenous ligands. Therefore, a thorough understanding of the intracellular trafficking properties of these ligands can lead to novel design criteria for engineering ligands to be more effective drug carriers. This review presents a few commonly used ligand/receptor systems where intracellular trafficking considerations can potentially improve the therapeutic efficacy of the ligand-drug molecular conjugates

Prediction of ovarian cancer prognosis and response to chemotherapy by a serum-based multiparametric biomarker panel

Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2. The odds ratio and hazard ratio and their 95% confidence interval (95% CI) were calculated. Time-dependent receiver-operating characteristic (ROC) curves were utilised to evaluate the prognostic performance of the biomarkers. The levels of several markers at baseline (c0), or after the first chemotherapy cycle (rc1), predicted chemotherapy response and overall or progression-free survival in univariate analysis. A multiparametric model (c0 of CA125, KLK5, KLK7 and rc1 of CA125) provided predictive accuracy with area under the ROC curve (AUC) of 0.82 (0.62 after correction for overfitting). Another marker combination (c0 of KLK7, KLK10, B7-H4, Spondin-2) was useful in predicting short-term (1-year) survival with an AUC of 0.89 (0.74 after correction for overfitting). All markers examined, except KLK7 and regenerating protein IV, were powerful predictors of time to progression (TTP) among chemotherapy responders. Individual and panels of biomarkers from the kallikrein family (and other families) can predict response to chemotherapy, overall survival, short-term (1-year) survival, progression-free survival and TTP of ovarian cancer patients treated with chemotherapy

Growth of single crystals in the (Na1/2Bi1/2)TiO3-(Sr1-xCax)TiO3 system by solid state crystal growth

Ceramics based on (Na1/2B1/2)TiO3 are promising candidates for actuator applications because of large strains generated by an electric field-induced phase transition. For example, the (1-x)(Na1/2Bi1/2)TiO3-xSrTiO(3) system exhibits a morphotropic phase boundary at x = 0.2-0.3, leading to high values of inverse piezoelectric constant d*(33), which can be further improved by the use of single crystals. In our previous work, single crystals of (Na1/2B1/2)TiO3-SrTiO3 and (Na1/2B1/2)TiO3-CaTiO3 were grown by the solid state crystal growth technique. Growth in the (Na1/2B1/2)TiO3-SrTiO3 system was sluggish whereas the (Na1/2B1/2)TiO3-CaTiO3 single crystals grew well. In the present work, 0.8(Na1/2Bi1/2)TiO3-0.2(Sr1-xCax)TiO3 single crystals (with x = 0.0, 0.1, 0.2, 0.3, 0.4) were produced by the solid state crystal growth technique in an attempt to improve crystal growth rate. The dependence of mean matrix grain size, single crystal growth distance, and electrical properties on the Ca concentration was investigated in detail. These investigations indicated that at x = 0.3 the matrix grain growth was suppressed and the driving force for single crystal growth was enhanced. Replacing Sr with Ca increased the shoulder temperature T-s and temperature of maximum relative permittivity T-max, causing a decrease in inverse piezoelectric properties and a change from normal to incipient ferroelectric behavior

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Cell-signalling dynamics in time and space

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Computational models provide insights into the intricate relationships between stimuli and responses and reveal mechanisms that enable networks to amplify signals, reduce noise and generate discontinuous bistable dynamics or oscillations. These temporal dynamics are coupled to precipitous spatial gradients of signalling activities, which guide pivotal intracellular processes, but also necessitate mechanisms to facilitate signal propagation across a cell