Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

Holocene development and anthropogenic disturbance of a shallow lake system in Central Ireland recorded by diatoms

Three cores from two connected lakes in Central Ireland (Lough Kinale and Derragh Lough) were investigated using diatom analysis to establish the Holocene development of the lacustrine system, any local variations within the lakes and any anthropogenic influences. The study area was situated in a lowland location and the lakes were shallow, unstratified and interconnected. Litho-and bio-stratigraphical analyses of the lake cores and deposits beneath a mire separating the two lakes showed the changing spatial configuration of the lake system in the early Holocene and the separation of the initial lake into three basins (cf. lacustrine cells) and finally into two interlinked lakes. The evolution of the lake system is conceptualised as the development of distinct lacustrine cells, and its sediments have recorded changes in the physical (geography, depth and sedimentation) and chemical (water chemistry) properties of the lakes inferred through diatom analyses. The longest sequence, from the early Holocene, records fluctuating lake levels and these are correlated with geomorphological mapping and surveying of palaeoshorelines. The diatom assemblages of the upper 2 m of the three cores, covering approximately the last 2000–3000 radiocarbon years show considerable difference in trophic status and life-form categories. This is related to the location of the cores in the lake and also the distance from human settlement with particular reference to proximity to crannog (artificial island) construction and use. The most central core from the deepest part of Lough Kinale has the least representation of the human settlement and agricultural activity in the catchment and on the fringes of the lake, whereas the core taken from the edge of a crannog is able to identify when construction and use of the crannog occurred. The local nature of the palaeoecological response to human activity due to incomplete water mixing has the advantage of allowing the lake sediment cores to be used to determine spatially discrete settlement patterns

Conservation: From Voluntary Restraint to a Voluntary Price Premium

Conservation behavior, Electricity demand, Renewable energy, D1, Q4, Q5,

ლელო N220 (2325)

პირველი ქართული სპორტული გაზეთ

Visualization, imaging and new preclinical diagnostics in radiation oncology

Innovative strategies in cancer radiotherapy are stimulated by the growing knowledge on cellular and molecular tumor biology, tumor pathophysiology, and tumor microenvironment. In terms of tumor diagnostics and therapy monitoring, the reliable delineation of tumor boundaries and the assessment of tumor heterogeneity are increasingly complemented by the non-invasive characterization of functional and molecular processes, moving preclinical and clinical imaging from solely assessing tumor morphology towards the visualization of physiological and pathophysiological processes. Functional and molecular imaging techniques allow for the non-invasive characterization of tissues in vivo, using different modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and optical imaging (OI). With novel therapeutic concepts combining optimized radiotherapy with molecularly targeted agents focusing on tumor cell proliferation, angiogenesis, and cell death, the non-invasive assessment of tumor microcirculation and tissue water diffusion, together with strategies for imaging the mechanisms of cellular injury and repair is of particular interest. Characterizing the tumor microenvironment prior to and in response to irradiation will help to optimize the outcome of radiotherapy. These novel concepts of personalized multi-modal cancer therapy require careful pre-treatment stratification as well as a timely and efficient therapy monitoring to maximize patient benefit on an individual basis. Functional and molecular imaging techniques are key in this regard to open novel opportunities for exploring and understanding the underlying mechanisms with the perspective to optimize therapeutic concepts and translate them into a personalized form of radiotherapy in the near future

Comparing Fuzzy and Probabilistic Approaches to Preference Uncertainty in Non-Market Valuation

Random utility maximization and fuzzy logic, Contingent valuation and preference uncertainty, c-Means clustering, Forest economics, Q51, C35,

Pesticidal plants for stored product pests on small-holder farms in Africa

Despite the near elimination of pests from food stores in industrialised nations, insects are still the most important challenge to food security for small-holder farmers in less developed nations. Losses are frequently as high as 20 %. Synthetic products provide effective control when used correctly but are not sustainable or universally appropriate and present many challenges for farmers, not least of all their cost. Pesticidal plants offer an economic, effective and often the only alternative. Much published research, however, overlooks critical knowledge gaps providing outputs that are unlikely to improve pesticidal plant use or improve food security. This chapter identifies opportunities for better targeted research and improvements for uptake and use of pesticidal plants. We also highlight how a deeper understanding of different morphs, gender and age of insect can influence experimental results and should be considered more carefully. To be effective plant materials need to show low animal and environmental toxicity at typical application levels but at the same time be effective against a wide range of target species, at low doses and with longevity. They must also be low cost, safe, compatible with other pest management technologies and stable and have no consequences for the stored products such as impairing flavour. Research should be targeted at optimising the efficacy of the pesticidal plants already known to have potential, and this should be supported by chemistry to fully understand spatial, temporal and phenotypic variability and nontarget impacts. Availability of plants is a limiting factor to uptake so propagation and cultivation of elite provenances would alleviate pressure on natural ecosystems and improve reliability of efficacy and supply when supported by improved harvesting techniques. The large-scale commercialisation of plants may not compete with synthetic products globally but local production may foster a mechanism to support and encourage uptake through local markets and value chains