200 research outputs found

    High-resolution water-quality and ecosystem-metabolism modeling in lowland rivers

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    High-resolution monitoring of water quality and ecosystem functioning over large spatial scales in expansive lowland river catchments is challenging. Therefore, we need modeling tools to predict these processes at locations where observations are absent. Here, we present a new approach to estimate ecosystem metabolism underpinned by a high-resolution, process-based model of in-stream flows and water quality. The model overcomes the current challenges in metabolism modeling by accounting for oxygen transport under varying flows and oxygen transformations due to biogeochemical processes. We implement the model in a 62-km-long stretch of the River Thames, England, using observations spanning 2 yr. Model outputs suggest that the river is primarily autotrophic from mid-spring to mid-summer due to high biomass during low-flow periods, and is heterotrophic during the rest of the year. Ecosystem respiration in upstream reaches is driven mainly by biochemical oxygen demand, autotrophic respiration, and nitrification processes, whereas downstream sites also show a control of benthic oxygen demand in addition to the aforementioned processes. Using empirical modeling, we analyze the sensitivity of our estimated metabolism rates to multiple environmental stressors. Results demonstrate that empirical models could be useful for rapid river health assessments, but need improvements to reproduce peak metabolism rates. The process-based model, although more complex than existing in situ approaches to metabolism quantification, allows inference when gaps in continuous observations are present. The model offers additional benefits for predicting metabolism rates under future scenarios of environmental change incorporating multiple stressor effects

    Is systems pharmacology ready to impact upon therapy development? A study of the cholesterol biosynthesis pathway.

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    Background and Purpose An ever-growing wealth of information on current drugs and their pharmacological effects is available from online databases. As our understanding of systems biology increases, we have the opportunity to predict, model and quantify how drug combinations can be introduced that outperform conventional single-drug therapies. Here, we explore the feasibility of such systems pharmacology approaches with an analysis of the mevalonate branch of the cholesterol biosynthesis pathway. Experimental Approach Using open online resources, we assembled a computational model of the mevalonate pathway and compiled a set of inhibitors directed against targets in this pathway. We used computational optimization to identify combination and dose options that show not only maximal efficacy of inhibition on the cholesterol producing branch but also minimal impact on the geranylation branch, known to mediate the side effects of pharmaceutical treatment. Key Results We describe serious impediments to systems pharmacology studies arising from limitations in the data, incomplete coverage and inconsistent reporting. By curating a more complete dataset, we demonstrate the utility of computational optimization for identifying multi-drug treatments with high efficacy and minimal off-target effects. Conclusion and Implications We suggest solutions that facilitate systems pharmacology studies, based on the introduction of standards for data capture that increase the power of experimental data. We propose a systems pharmacology workflow for the refinement of data and the generation of future therapeutic hypotheses

    Subduction or sagduction? Ambiguity in constraining the origin of ultramafic–mafic bodies in the Archean crust of NW Scotland

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    The Lewisian Complex of NW Scotland is a fragment of the North Atlantic Craton. It comprises mostly Archean tonalite–trondhjemite–granodiorite (TTG) orthogneisses that were variably metamorphosed and reworked in the late Neoarchean to Paleoproterozoic. Within the granulite facies central region of the mainland Lewisian Complex, discontinuous belts composed of ultramafic–mafic rocks and structurally overlying garnet–biotite gneiss (brown gneiss) are spatially associated with steeply-inclined amphibolite facies shear zones that have been interpreted as terrane boundaries. Interpretation of the primary chemical composition of these rocks is complicated by partial melting and melt loss during granulite facies metamorphism, and contamination with melts derived from the adjacent migmatitic TTG host rocks. Notwithstanding, the composition of the layered ultramafic–mafic rocks is suggestive of a protolith formed by differentiation of tholeiitic magma, where the ultramafic portions of these bodies represent the metamorphosed cumulates and the mafic portions the metamorphosed fractionated liquids. Although the composition of the brown gneiss does not clearly discriminate the protolith, it most likely represents a metamorphosed sedimentary or volcano-sedimentary sequence. For Archean rocks, particularly those metamorphosed to granulite facies, the geochemical characteristics typically used for discrimination of paleotectonic environments are neither strictly appropriate nor clearly diagnostic. Many of the rocks in the Lewisian Complex have ‘arc-like’ trace element signatures. These signatures are interpreted to reflect derivation from hydrated enriched mantle and, in the case of the TTG gneisses, partial melting of amphibolite source rocks containing garnet and a Ti-rich phase, probably rutile. However, it is becoming increasingly recognised that in Archean rocks such signatures may not be unique to a subduction environment but may relate to processes such as delamination and dripping. Consequently, it is unclear whether the Lewisian ultramafic–mafic rocks and brown gneisses represent products of plate margin or intraplate magmatism. Although a subduction-related origin is possible, we propose that an intraplate origin is equally plausible. If the second alternative is correct, the ultramafic–mafic rocks and brown gneisses may represent the remnants of intracratonic greenstone belts that sank into the deep crust due to their density contrast with the underlying partially molten low viscosity TTG orthogneisses

    Realising consilience: How better communication between archaeologists, historians and natural scientists can transform the study of past climate change in the Mediterranean

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    This paper reviews the methodological and practical issues relevant to the ways in which natural scientists, historians and archaeologists may collaborate in the study of past climatic changes in the Mediterranean basin. We begin by discussing the methodologies of these three disciplines in the context of the consilience debate, that is, attempts to unify different research methodologies that address similar problems. We demonstrate that there are a number of similarities in the fundamental methodology between history, archaeology, and the natural sciences that deal with the past (“palaeoenvironmental sciences”), due to their common interest in studying societal and environmental phenomena that no longer exist. The three research traditions, for instance, employ specific narrative structures as a means of communicating research results. We thus present and compare the narratives characteristic of each discipline; in order to engage in fruitful interdisciplinary exchange, we must first understand how each deals with the societal impacts of climatic change. In the second part of the paper, we focus our discussion on the four major practical issues that hinder communication between the three disciplines. These include terminological misunderstandings, problems relevant to project design, divergences in publication cultures, and differing views on the impact of research. Among other recommendations, we suggest that scholars from the three disciplines should aim to create a joint publication culture, which should also appeal to a wider public, both inside and outside of academia.This paper emerged as a result of a workshop at Costa Navarino and the Navarino Environmental Observatory (NEO), Greece in April 2014, which addressed Mediterranean Holocene climate and human societies. The workshop was co-sponsored by IGBP/PAGES, NEO, the MISTRALS/PaleoMex program, the Labex OT-Med, the Bolin Centre for Climate Research at Stockholm University, and the Institute of Oceanography at the Hellenic Centre for Marine Research. We also acknowledge funding from the National Science Centre, Poland, within the scheme of the Centre's postdoctoral fellowships (DEC-2012/04/S/HS3/00226 (A.I)); the Swedish Research Council (grant numbers 421-2014-1181 (E.W.) and 621-2012-4344 (K.H.)); CSIC-Ramón y Cajal post-doctoral program RYC-2013-14073 and Clare Hall College, Cambridge, Shackleton Fellowship (B.M.); the EU/FP7 Project ‘Sea for Society’ (Science and Society - 2011-1, 289066)

    Lasers and ancillary treatments for scar management Part 2: Keloid, hypertrophic, pigmented and acne scars

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    The formation of a wide range of excessive scars following various skin injuries is a natural consequence of healing. Scars resulting from surgery or trauma affect approximately 100 million people per annum in the developed world and can have profound physical, aesthetic, psychological and social consequences. Thus, scar treatment is a priority for patient and physician alike. Laser treatment plays an important role in scar management with additional support from ancillary modalities. Subsequent to part 1: Burns scars, part 2 focuses on our strategies and literature review of treatment of keloid, hypertrophic, pigmented and acne scars where lasers are used in conjunction with other measures, and illustrated with case studies

    Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

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    Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

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    The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

    Mutation Testing Advances: An Analysis and Survey

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