Biochemical studies of the tracheobronchial epithelium.

Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. In brief, formidable strides have been made in biochemistry specific to this important target tissue, despite the inability to acquire tracheobronchial epithelium in large quantities

Growth, profits and technological choice: The case of the Lancashire cotton textile industry

Using Lancashire textile industry company case studies and financial records, mainly from the period just before the First World War, the processes of growth and decline are re-examined. These are considered by reference to the nature of Lancashire entrepreneurship and the impact on technological choice. Capital accumulation, associated wealth distributions and the character of Lancashire business organisation were sybiotically linked to the success of the industry before 1914. However, the legacy of that accumulation in later decades, chronic overcapacity, formed a barrier to reconstruction and enhanced the preciptious decline of a once great industry

Ensemble prediction for nowcasting with a convection-permitting model—I: description of the system and the impact of radar-derived surface precipitation rates

A key strategy to improve the skill of quantitative predictions of precipitation, as well as hazardous weather such as severe thunderstorms and flash floods is to exploit the use of observations of convective activity (e.g. from radar). In this paper, a convection-permitting ensemble prediction system (EPS) aimed at addressing the problems of forecasting localized weather events with relatively short predictability time scale and based on a 1.5 km grid-length version of the Met Office Unified Model is presented. Particular attention is given to the impact of using predicted observations of radar-derived precipitation intensity in the ensemble transform Kalman filter (ETKF) used within the EPS. Our initial results based on the use of a 24-member ensemble of forecasts for two summer case studies show that the convective-scale EPS produces fairly reliable forecasts of temperature, horizontal winds and relative humidity at 1 h lead time, as evident from the inspection of rank histograms. On the other hand, the rank histograms seem also to show that the EPS generates too much spread for forecasts of (i) surface pressure and (ii) surface precipitation intensity. These may indicate that for (i) the value of surface pressure observation error standard deviation used to generate surface pressure rank histograms is too large and for (ii) may be the result of non-Gaussian precipitation observation errors. However, further investigations are needed to better understand these findings. Finally, the inclusion of predicted observations of precipitation from radar in the 24-member EPS considered in this paper does not seem to improve the 1-h lead time forecast skill

Integrate and Fire Neural Networks, Piecewise Contractive Maps and Limit Cycles

We study the global dynamics of integrate and fire neural networks composed of an arbitrary number of identical neurons interacting by inhibition and excitation. We prove that if the interactions are strong enough, then the support of the stable asymptotic dynamics consists of limit cycles. We also find sufficient conditions for the synchronization of networks containing excitatory neurons. The proofs are based on the analysis of the equivalent dynamics of a piecewise continuous Poincar\'e map associated to the system. We show that for strong interactions the Poincar\'e map is piecewise contractive. Using this contraction property, we prove that there exist a countable number of limit cycles attracting all the orbits dropping into the stable subset of the phase space. This result applies not only to the Poincar\'e map under study, but also to a wide class of general n-dimensional piecewise contractive maps.Comment: 46 pages. In this version we added many comments suggested by the referees all along the paper, we changed the introduction and the section containing the conclusions. The final version will appear in Journal of Mathematical Biology of SPRINGER and will be available at http://www.springerlink.com/content/0303-681

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Associative memory storing an extensive number of patterns based on a network of oscillators with distributed natural frequencies in the presence of external white noise

We study associative memory based on temporal coding in which successful retrieval is realized as an entrainment in a network of simple phase oscillators with distributed natural frequencies under the influence of white noise. The memory patterns are assumed to be given by uniformly distributed random numbers on $[0,2\pi)$ so that the patterns encode the phase differences of the oscillators. To derive the macroscopic order parameter equations for the network with an extensive number of stored patterns, we introduce the effective transfer function by assuming the fixed-point equation of the form of the TAP equation, which describes the time-averaged output as a function of the effective time-averaged local field. Properties of the networks associated with synchronization phenomena for a discrete symmetric natural frequency distribution with three frequency components are studied based on the order parameter equations, and are shown to be in good agreement with the results of numerical simulations. Two types of retrieval states are found to occur with respect to the degree of synchronization, when the size of the width of the natural frequency distribution is changed.Comment: published in Phys. Rev.

Cathodoluminescence study of ZnO wafers cut from hydrothermal crystals

ZnO is a wide bandgap semiconductor with very promising expectation for UV optoelectronics. The existence of large crystals should allow homoepitaxial growth of ZnO films for advanced optoelectronic devices. However, the ZnO substrates are not yet mature. Both defect induced by growth and by polishing together with the high reactivity of the surface are problems to their industrial application. Cathodoluminescence (CL) was used to probe the quality of substrates from two different suppliers. The surface damage was studied by varying the penetration depth of the electron beam, allowing to observe significant differences between the two samples within a 0.5-mm-thick surface layer. CL spectra show a complex band (P1) at _3.3 eV composed of two overlapped bands (3.31 and 3.29 eV) related to point defects (PD) and the 1-LO phonon replica of the free exciton (FX-1LO). This band (P1) is shown to be very sensitive to the presence of defects and the surface and thermal treatments. Its intensity compared with the excitonic band intensity is demonstrated to provide criteria about the quality of the substrates

Non-equilibrium stationary state of a two-temperature spin chain

A kinetic one-dimensional Ising model is coupled to two heat baths, such that spins at even (odd) lattice sites experience a temperature $T_{e}$ ($$). Spin flips occur with Glauber-type rates generalised to the case of two temperatures. Driven by the temperature differential, the spin chain settles into a non-equilibrium steady state which corresponds to the stationary solution of a master equation. We construct a perturbation expansion of this master equation in terms of the temperature difference and compute explicitly the first two corrections to the equilibrium Boltzmann distribution. The key result is the emergence of additional spin operators in the steady state, increasing in spatial range and order of spin products. We comment on the violation of detailed balance and entropy production in the steady state.Comment: 11 pages, 1 figure, Revte