Proteomic analysis of cell models of ovarian cancer tumour suppression

Epithelial ovarian cancer (EOC) is the most common form of gynaecological malignancy in the developed world. Identifying molecular markers of disease may provide novel approaches to screening and could enable targeted treatment and the design of novel therapies. In previous work, 141 primary ovarian tumours were analysed using metaphase comparative genomic hybridization to identify complete or partial chromosome deletions that may harbour tumour and/or metastasis suppressor genes. Chromosome 18 (Ch18) was found to have deletions in 50% of the tumours. Microcell-mediated chromosome transfer (MMCT) of normal Ch18 material into EOC cell lines resulted in hybrids that displayed significant suppression of anchorageindependent growth, invasiveness and reduced tumour growth in nude mice. The major aim of this project was to identify protein changes associated with the tumour suppression observed in the EOC Ch18 MMCT cell models. The project involves a detailed quantitative proteomic comparison of two parental ovarian cancer cell lines (derived from primary endometrioid and clear cell carcinomas) and their MMCT-derived Ch18 hybrid clones. The cellular, secreted and surface proteomes were probed in order to gain comprehensive coverage and to improve the likelihood of useful biomarker identification. A combination of quantitative two-dimensional difference gel electrophoresis (2DDIGE), affinity chromatography and two-dimensional-liquid chromatography and tandem mass spectrometry (2D-LC-MS/MS) have been employed to examine the whole cell, secreted and cell surface proteomes of the parental and hybrid cell models to identify differentially expressed proteins as potential markers of tumour suppression. Proteins of interest have been validated using immune-based detection methods in the parental cell lines, Ch18 hybrids, revertant cell lines, a panel of cancer cell lines and normal ovarian surface epithelium cell lines and in serum from a set of ovarian cancer cases and healthy controls

Correlation Functions for \beta=1 Ensembles of Matrices of Odd Size

Using the method of Tracy and Widom we rederive the correlation functions for \beta=1 Hermitian and real asymmetric ensembles of N x N matrices with N odd.Comment: 15 page

Virtual embedded librarianship for information literacy teaching.

This paper, reports on the planning and preliminary results of an action research project undertaken for the redesign of an online distance learning information literacy (IL) module on the basis of virtual 'embedded librarianship'. The research project, which followed an action research design, brought together the IL module coordinator and an Academic Liaison Librarian, working at different institutions to collaboratively redesign the assessment and teaching of the module. Data were collected via a qualitative analysis of students' work and a series of open-ended questions addressed to students on the value of the approach followed. Students reacted positively to the embedded librarianship design and engaged constructively in situated learning. Challenges included time-zones differences, the contribution level of students and lack of confidence. The paper puts emphasis on educating future information professionals as embedded information literacy partners, promoting the development of transferable skills and a collaborative/sharing online working ethos

Local minimal energy landscapes in river networks

The existence and stability of the universality class associated to local minimal energy landscapes is investigated. Using extensive numerical simulations, we first study the dependence on a parameter $\gamma$ of a partial differential equation which was proposed to describe the evolution of a rugged landscape toward a local minimum of the dissipated energy. We then compare the results with those obtained by an evolution scheme based on a variational principle (the optimal channel networks). It is found that both models yield qualitatively similar river patterns and similar dependence on $\gamma$. The aggregation mechanism is however strongly dependent on the value of $\gamma$. A careful analysis suggests that scaling behaviors may weakly depend both on $\gamma$ and on initial condition, but in all cases it is within observational data predictions. Consequences of our resultsComment: 12 pages, 13 figures, revtex+epsfig style, to appear in Phys. Rev. E (Nov. 2000

Fatty acid metabolism in marine fish: Low activity of fatty acyl Δ5 desaturation in gilthead sea bream ( Sparus aurata ) cells

Marine fish are known to have an absolute dietary requirement for C20 and C22 highly unsaturated fatty acids. Previous studies using cultured cell lines indicated that underlying this requirement in marine fish was either a deficiency in fatty acyl Δ5 desaturase or C18-20 elongase activity. Recently, Ghioni et al. (Biochim. Biophys. Acta, 1437, 170-181, 1999) presented evidence that in turbot cells there was low activity of C18-20 elongase whereas Δ5 desaturase had high activity. In the present study, the fatty acid desaturase/elongase pathway was investigated in a cell line (SAF-1) from another carnivorous marine fish, sea bream. The metabolic conversions of a range of radiolabelled polyunsaturated fatty acids that comprised the direct substrates for Δ6 desaturase ([1-14C]18:2n-6 and [1-14C]18:3n-3), C18-20 elongase ([U-14C]18:4n-3), Δ5 desaturase ([1-14C]20:3n-6 and [U-14C]20:4n-3) and C20-22 elongase ([1-14C]20:4n-6 and [1-14C]20:5n-3) were utilized. The results showed that fatty acyl Δ6 desaturase in SAF-1 cells was highly active and there was substantial C18-20 elongase and C20-22 elongase activities. A deficiency in the desaturation/elongation pathway was clearly identified at the level of the fatty acyl Δ5 desaturase which was very low, particularly with 20:4n-3 as substrate. In comparison, the apparent activities of Δ6 desaturase, C18-20 elongase and C20-22 elongase were approximately 94-fold, 27-fold and 16-fold greater than that for Δ5 desaturase towards their respective n-3 polyunsaturated fatty acid substrates. The evidence obtained in the SAF-1 cell line is consistent with the dietary requirement for C20 and C22 highly unsaturated fatty acids in the marine fish, the sea bream, being primarily due to a deficiency in fatty acid Δ5 desaturase activity

Real-time measurement of metabolic rate during freezing and thawing of the wood frog, Rana sylvatica: Implications for overwinter energy use

Ectotherms overwintering in temperate ecosystems must survive low temperatures while conserving energy to fuel post-winter reproduction. Freeze-tolerant wood frogs, Rana sylvatica, have an active response to the initiation of ice formation that includes mobilising glucose from glycogen and circulating it around the body to act as a cryoprotectant. We used flow-through respirometry to measure CO2 production (VCO2) in real time during cooling, freezing and thawing. CO2 production increases sharply at three points during freeze-thaw: at +1°C during cooling prior to ice formation (total of 104±17 μl CO2 frog-1 event-1), at the initiation of freezing (565±85 μl CO 2 frog-1 freezing event-1) and after the frog has thawed (564±75 μl CO2 frog-1 freezing event-1). We interpret these increases in metabolic rate to represent the energetic costs of preparation for freezing, the response to freezing and the re-establishment of homeostasis and repair of damage after thawing, respectively. We assumed that frogs metabolise lipid when unfrozen and that carbohydrate fuels metabolism during cooling, freezing and thawing, and when frozen. We then used microclimate temperature data to predict overwinter energetics of wood frogs. Based on the freezing and melting points we measured, frogs in the field were predicted to experience as many as 23 freeze-thaw cycles in the winter of our microclimate recordings. Overwinter carbohydrate consumption appears to be driven by the frequency of freeze-thaw events, and changes in overwinter climate that affect the frequency of freeze-thaw will influence carbohydrate consumption, but changes that affect mean temperatures and the frequency of winter warm spells will modify lipid consumption

The calibration system for the photomultiplier array of the SNO+ experiment

A light injection system using LEDs and optical fibres was designed for the calibration and monitoring of the photomultiplier array of the SNO+ experiment at SNOLAB. Large volume, non-segmented, low-background detectors for rare event physics, such as the multi-purpose SNO+ experiment, need a calibration system that allow an accurate and regular measurement of the performance parameters of their photomultiplier arrays, while minimising the risk of radioactivity ingress. The design implemented for SNO+ uses a set of optical fibres to inject light pulses from external LEDs into the detector. The design, fabrication and installation of this light injection system, as well as the first commissioning tests, are described in this paper. Monte Carlo simulations were compared with the commissioning test results, confirming that the system meets the performance requirements

Archaeological signatures of landscape and settlement change on the Isle of Harris

Between 2004 and 2011, a programme of archaeological investigation by the University of Birmingham on the Isle of Harris, a distinctive island forming part of the Western Isles of Scotland, has allowed the archaeological remains of this enigmatic place to be further characterised and understood. Despite intensive archaeological interest in the archipelago for a number of decades, the Isle of Harris has been overlooked and only now are we beginning to identify the archaeological resource and make comparisons to the wealth of published data from islands such as the Uists, Barra and Lewis. This paper highlights some generic overall patterns of archaeological signatures on the Isle which has been identified through a range of archaeological methods including field walking, intrusive excavation, aerial reconnaissance, geophysical and topographical survey, and documentary research. Several key case studies will be introduced including upland shieling complexes and mulitperiod settlement sites on the west coast machair systems. The purpose of the paper is not to present a gazetteer of the results of the work to date, but to highlight some of the key findings with a view to demonstrating that the Isle of Harris is directly comparable with the archaeologically rich landscapes of the other islands

History and Applications of Dust Devil Studies

Studies of dust devils, and their impact on society, are reviewed. Dust devils have been noted since antiquity, and have been documented in many countries, as well as on the planet Mars. As time-variable vortex entities, they have become a cultural motif. Three major stimuli of dust devil research are identified, nuclear testing, terrestrial climate studies, and perhaps most significantly, Mars research. Dust devils present an occasional safety hazard to light structures and have caused several deaths

Scale issues in soil moisture modelling: problems and prospects

Soil moisture storage is an important component of the hydrological cycle and plays a key role in land-surface-atmosphere interaction. The soil-moisture storage equation in this study considers precipitation as an input and soil moisture as a residual term for runoff and evapotranspiration. A number of models have been developed to estimate soil moisture storage and the components of the soil-moisture storage equation. A detailed discussion of the impli cation of the scale of application of these models reports that it is not possible to extrapolate processes and their estimates from the small to the large scale. It is also noted that physically based models for small-scale applications are sufficiently detailed to reproduce land-surface- atmosphere interactions. On the other hand, models for large-scale applications oversimplify the processes. Recently developed physically based models for large-scale applications can only be applied to limited uses because of data restrictions and the problems associated with land surface characterization. It is reported that remote sensing can play an important role in over coming the problems related to the unavailability of data and the land surface characterization of large-scale applications of these physically based models when estimating soil moisture storage.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline