404 research outputs found

    Collecting Critical Data to Assess the Sustainability of Rural Infrastructure in Low-Income Countries

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    Rural water systems in low-income countries often fail to deliver potable water sustainably.Reasons include socio-economic, financial, and technical challenges that are specific to the community. Improved assessment methods are critical if decision makers want to provide sustainable solutions; however, to be useful, such methods require substantial data about the complex interaction between people, water, and infrastructure. Such interaction is affected by, and in turn, affects the behavior of community members regarding water usage, resources for infrastructure maintenance, and choice of assets. Unfortunately, much of these data are not readily available, in a large part because of the site-specific context associated with each rural community. Because of the difficulty and expense in obtaining site-specific data, it is important to identify the most critical needs for field studies versus the data that can be obtained from sources such as non-governmental organizations and the general literature.We examine this issue by first using an extensive data set from Malawi to identify the critical data needs. We then present several examples of field studies in Honduras and Uganda where we collected some of that critical data. Throughout, we discuss best practices for conducting and using focused field studies versus the general literature

    Phylogeny and biogeography of the Pleistocene Holarctic steppe and semidesert goosefoot plant Krascheninnikovia ceratoides

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    Krascheninnikovia ceratoides (Chenopodiaceae) is a steppe and semi-desert plant with two subspecies, K. ceratoides subsp. ceratoides, which is widespread in Eurasia, and K. ceratoides subsp. lanata, which grows in western and central North America. A few disjunct populations of K. ceratoides subsp. ceratoides are found in Anatolia, Europe and North Africa to the west of its otherwise continuous Eurasian distribution. To understand the evolutionary history of this characteristic steppe and semi-desert plant, we analysed its phylogeny and biogeography. We sequenced several loci including ITS, ETS and the chloroplast intergenic spacer regions atpB-rbcL, rpl32-trnL and trnL-trnF to establish a time-calibrated phylogeny and reconstruct intraspecific relationships. Furthermore, we identified the ploidy level of individuals. While diploid, tetraploid and hexaploid individuals have been reported in the literature, we were only able to find diploids and tetraploids. The diploids were found in the east of Mongolia, Kazakhstan, Kyrgyzstan, Russia and the USA. The tetraploids were located in the west of Mongolia, Kazakhstan, Tajikistan, Russia, and Europe. Populations were uniformly di- or tetraploid. Our results indicate that the species may have spread from the area of Mongolia, northern China and Middle Asia (i.e., the Altai Mountains region) in two opposite directions – on the one hand, diploids migrated to the east, to eastern Asia and North America, and on the other hand diploids and tetraploids migrated to the west, to western Asia and Europe. Fossil-calibrated gene trees were used to estimate the age of the species. Diversification within the species is probably of Pleistocene age. Our dated analysis indicates that the first split among extant lineages of the species took place in the Early Pleistocene (Gelasian). The spread of the main lineages is likely related to major phases of steppe and semi-desert expansions during glacial periods of the Pleistocene

    Characterization of cytochrome P450 CYP109E1 from Bacillus megaterium as a novel vitamin D3 hydroxylase

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    In this study the ability of CYP109E1 from Bacillus megaterium to metabolize vitamin D3 (VD3) was investigated. In an in vitro system using bovine adrenodoxin reductase (AdR) and adrenodoxin (Adx4-108), VD3 was converted by CYP109E1 into several products. Furthermore, a whole-cell system in B. megaterium MS941 was established. The new system showed a conversion of 95% after 24h. By NMR analysis it was found that CYP109E1 catalyzes hydroxylation of VD3 at carbons C-24 and C-25, resulting in the formation of 24(S)-hydroxyvitamin D3 (24S(OH)VD3), 25-hydroxyvitamin D3 (25(OH)VD3) and 24S,25-dihydroxyvitamin D3 (24S,25(OH)2VD3). Through time dependent whole-cell conversion of VD3, we identified that the formation of 24S,25(OH)2VD3 by CYP109E1 is derived from VD3 via the intermediate 24S(OH)VD3. Moreover, using docking analysis and site-directed mutagenesis, we identified important active site residues capable of determining substrate specificity and regio-selectivity. HPLC analysis of the whole-cell conversion with the I85A-mutant revealed an increased selectivity towards 25-hydroxylation of VD3 compared with the wild type activity, resulting in an approximately 2-fold increase of 25(OH)VD3 production (45mgl(-1)day(-1)) compared to wild type (24.5mgl(-1)day(-1))

    Early Miocene tectono-sedimentary shift in the eastern North Alpine Foreland Basin and its relation to changes in tectonic style in the Eastern Alps

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    A striking difference along the Alpine Orogen is the style of collisional tectonics during the Oligo-Miocene, with the onset of escape tectonics in the Eastern Alps (Fig. 1A). The indentation of the Adriatic Plate into the Eastern Alpine Orogen resulted in the formation of conjugate dextral and sinistral strike-slip faults in the vicinity of the Tauern Window. Moreover, major changes occurred in the foreland of the Eastern and Southern Alps in the Early Miocene, with the cessation of the northern Alpine front propagation and the onset of thrusting along the Southern Alpine Front. In this study, we present new results from structural, stratigraphic and subsidence analyses of the eastern North Alpine Foreland Basin (NAFB; Fig. 1B) as part of the “Mountain Building in 4 Dimensions” project, German branch of the European AlpArray initiative, which aims at better understanding the deep crustal-mantle structures of the Alpine Orogen and their relation to surface processes. Our results show a first phase of onset of foreland sedimentation in the eastern NAFB between c. 33-28 Ma, followed by a strong tectonic-driven subsidence between c. 28-25 Ma ending by a phase of erosion and the formation of a basin-wide Northern Slope Unconformity (NSU; Fig. 1C & 1D). During this time period, the rift-related Mesozoic normal faults of the European platform were reactivated and are capped by the NSU (Fig. 1D). We interpret this phase as an increase in the flexure of the subducting European Plate under the growing Alpine Orogen. Between 25-19 Ma, the eastern NAFB remained in a deep-marine, underfilled state with a gently increase in subsidence. A major shift took place around 19-17 Ma with strong tectonic-driven uplift, ranging from 200 m (absolute minimum) to 1200 m depending on uncertainties on paleo-water depths, and rapid sedimentary infill of the basin (Fig. 1C & 1D). We discuss the possible causes for this major tectono-sedimentary shift in the eastern NAFB in relation to contemporaneous changes in collisional tectonics within the Eastern and Southern Alps, and with a potential Early Miocene slab break-off event beneath the Eastern Alps

    Spin Crossover in a Hexaamineiron(II) Complex: Experimental Confirmation of a Computational Prediction

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    Single crystal structural analysis of [Fe^II(tame)_2]Cl_2⋅MeOH (tame=1,1,1‐tris(aminomethyl)ethane) as a function of temperature reveals a smooth crossover between a high temperature high‐spin octahedral d^6 state and a low temperature low‐spin ground state without change of the symmetry of the crystal structure. The temperature at which the high and low spin states are present in equal proportions is T_1/2=140 K. Single crystal, variable‐temperature optical spectroscopy of [Fe^II(tame)_2]Cl_2⋅MeOH is consistent with this change in electronic ground state. These experimental results confirm the spin activity predicted for [Fe^II(tame)_2]^2+ during its de novo artificial evolution design as a spin‐crossover complex [Chem. Inf. Model . 2015 , 55 , 1844], offering the first experimental validation of a functional transition‐metal complex predicted by such in silico molecular design methods. Additional quantum chemical calculations offer, together with the crystal structure analysis, insight into the role of spin‐passive structural components. A thermodynamic analysis based on an Ising‐like mean field model (Slichter–Drickammer approximation) provides estimates of the enthalpy, entropy and cooperativity of the crossover between the high and low spin states.publishedVersio

    EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands

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    The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.</p

    Regio- and stereoselective steroid hydroxylation by CYP109A2 from Bacillus megaterium explored by X-ray crystallography and computational modeling

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    The P450 monooxygenase CYP109A2 from Bacillus megaterium DSM319 was previously found to convert vitamin D3 to 25-hydroxyvitamin D3. Here, we show that this enzyme is also able to convert testosterone in a highly regio- and stereoselective manner to 16β-hydroxytestosterone. To reveal the structural determinants governing the regio- and stereoselective steroid hydroxylation reactions catalyzed by CYP109A2, two crystal structures of CYP109A2 were solved in similar closed conformations, one revealing a bound testosterone in the active site pocket, albeit at a non-productive site away from the heme-iron. To examine if the closed crystal structures nevertheless correspond to a reactive conformation of CYP109A2, docking and molecular dynamics simulations were performed with testosterone and vitamin D3 present in the active site. These molecular dynamics simulations were analyzed for catalytically productive conformations, the relative occurrences of which were in agreement with the experimentally determined stereoselectivities if the predicted stability of each carbon hydrogen bond was taken into account. Overall, the first-time determination and analysis of the catalytically relevant 3D conformation of CYP109A2 will allow for future small molecule ligand screening in silico, as well as enabling site-directed mutagenesis towards improved enzymatic properties of this enzyme.</p

    Oregon Downtown Development Association's resource team report for Hubbard, Oregon

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    102 pp. Bookmarks supplied by UO. Published June 26, 2003. Captured June 8, 2006.This report is a summary of information collected and synthesized by the ODDA Resource Team while working in Hubbard May 24-26, 2003. It is based on the information presented at the May 26th final presentation. The recommendations in this report are broken into sections based on the team members' specialties: Public Space and Architectural Design; Downtown Business Mix and Clustering; and Next Steps. [From the Plan]The Hubbard Resource Team and Report were funded through a partnership between Hubbard Businesses and the Mid-Willamette Valley Council of Government’s Regional Strategies Funds

    The psychological correlates of distinct neural states occurring during wakeful rest

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    When unoccupied by an explicit external task, humans engage in a wide range of different types of self-generated thinking. These are often unrelated to the immediate environment and have unique psychological features. Although contemporary perspectives on ongoing thought recognise the heterogeneity of these self-generated states, we lack both a clear understanding of how to classify the specific states, and how they can be mapped empirically. In the current study, we capitalise on advances in machine learning that allow continuous neural data to be divided into a set of distinct temporally re-occurring patterns, or states. We applied this technique to a large set of resting state data in which we also acquired retrospective descriptions of the participants' experiences during the scan. We found that two of the identified states were predictive of patterns of thinking at rest. One state highlighted a pattern of neural activity commonly seen during demanding tasks, and the time individuals spent in this state was associated with descriptions of experience focused on problem solving in the future. A second state was associated with patterns of activity that are commonly seen under less demanding conditions, and the time spent in it was linked to reports of intrusive thoughts about the past. Finally, we found that these two neural states tended to fall at either end of a neural hierarchy that is thought to reflect the brain's response to cognitive demands. Together, these results demonstrate that approaches which take advantage of time-varying changes in neural function can play an important role in understanding the repertoire of self-generated states. Moreover, they establish that important features of self-generated ongoing experience are related to variation along a similar vein to those seen when the brain responds to cognitive task demands
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