The sedimentology and diagenesis of Lower Permian (Rotliegend) sediments: (onshore U.K. and southern North Sea). Available in 2 volumes.

The thesis provides a comparative study of both sedimentology and diagenesis of Lower Permian (Rotliegend) strata, onshore and offshore U.K. (Southern North Sea). Onshore formations studied include the Bridgnorth, Penrith and Hopeman Sandstone, and are dominated by aeolian facies, with lesser amounts of interbedded fluvial sediments. Aeolian and fluvial strata in onshore basins typically grade laterally into alluvial fan breccias at basin margins. Onshore basins represent proximal examples of Rotliegend desert sediments. The Leman Sandstone Formation of the Ravenspurn area in the Southern North Sea displays a variety of facies indicative of a distal sedimentological setting; Aeolian, fluvial, sabkha, and playa lake sediments all being present. "Sheet-like" geometry of stratigraphical units within the Leman Sandstone, and alternation of fluvial and aeolian deposition was climatically controlled. Major first order bounding surfaces are laterally extensive and were produced by lacustrine transgression and regression from the north-west. Diagenesis within Permian strata was studied using standard petrographic microscopy, scanning electron microscopy, cold cathodo-Iuminescence, X-ray diffraction clay analysis, X-ray fluorescence spectroscopy, fluid inclusion microthermometry, and K-Ar dating of illites. The diagenesis of Permian sediments within onshore basins is remarkably similar, and a paragenetic sequence of early haematite, illitic clays, feldspar, kaolinite, quartz and late calcite is observed. In the Leman Sandstone formation, authigenic mineralogy is complex and includes early quartz, sulphates and dolomite, chlorite, kaolinite, late quartz, illite and siderite. Primary lithological variation, facies type, and the interdigitation and location of facies within a basin are important initial controls upon diagenesis. Subsequently, burial history, structure, the timing of gas emplacement, and the nature of sediments within underlying formations may also exersize significant controls upon diagenesis within Rotliegend strata.

Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance.