Contributions to uncertainty related to hydrostratigraphic modeling using multiple-point statistics

Forecasting the flow of groundwater requires a hydrostratigraphic model, which describes the architecture of the subsurface. State-of-the-art multiple-point statistical (MPS) tools are readily available for creating models depicting subsurface geology. We present a study of the impact of key parameters related to stochastic MPS simulation of a real-world hydrogeophysical dataset from Kasted, Denmark, using the snesim algorithm. The goal is to study how changes to the underlying datasets propagate into the hydrostratigraphic realizations when using MPS for stochastic modeling. This study focuses on the sensitivity of the MPS realizations to the geophysical soft data, borehole lithology logs, and the training image (TI). The modeling approach used in this paper utilizes a cognitive geological model as a TI to simulate ensemble hydrostratigraphic models. The target model contains three overall hydrostratigraphic categories, and the MPS realizations are compared visually as well as quantitatively using mathematical measures of similarity. The quantitative similarity analysis is carried out exhaustively, and realizations are compared with each other as well as with the cognitive geological model.The results underline the importance of geophysical data for constraining MPS simulations. Relying only on borehole data and the conceptual geology, or TI, results in a significant increase in realization uncertainty. The airborne transient electromagnetic SkyTEM data used in this study cover a large portion of the Kasted model area and are essential to the hydrostratigraphic architecture. On the other hand, the borehole lithology logs are sparser, and 410 boreholes were present in this study. The borehole lithology logs infer local changes in the immediate vicinity of the boreholes, thus, in areas with a high degree of geological heterogeneity, boreholes only provide limited large-scale structural information. Lithological information is, however, important for the interpretation of the geophysical responses. The importance of the TI was also studied. An example was presented where an alternative geological model from a neighboring area was used to simulate hydrostratigraphic models. It was shown that as long as the geological settings are similar in nature, the realizations, although different, still reflect the hydrostratigraphic architecture. If a TI containing a biased geological conceptualization is used, the resulting realizations will resemble the TI and contain less structure in particular areas, where the soft data show almost even probability to two or all three of the hydrostratigraphic units.</p

First molecular phylogenetic insights into the evolution of Eriocaulon (Eriocaulaceae, Poales)

Eriocaulon is a genus of c. 470 aquatic and wetland species of the monocot plant family Eriocaulaceae. It is widely distributed in Africa, Asia and America, with centres of species richness in the tropics. Most species of Eriocaulon grow in wetlands although some inhabit shallow rivers and streams with an apparent adaptive morphology of elongated submerged stems. In a previous molecular phylogenetic hypothesis, Eriocaulon was recovered as sister of the African endemic genus Mesanthemum. Several regional infrageneric classifications have been proposed for Eriocaulon. This study aims to critically assess the existing infrageneric classifications through phylogenetic reconstruction of infrageneric relationships, based on DNA sequence data of four chloroplast markers and one nuclear marker. There is little congruence between our molecular results and previous morphology-based infrageneric classifications. However, some similarities can be found, including Fyson’s sect. Leucantherae and Zhang’s sect. Apoda. Further phylogenetic studies, particularly focusing on less well sampled regions such as the Neotropics, will help provide a more global overview of the relationships in Eriocaulon and may enable suggesting the first global infrageneric classification

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites

The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed PEXEL cleavage occurs cotranslationaly, similar to signal peptidase. Treatment of P. falciparum-infected erythrocytes with the inhibitor caused dose-dependent inhibition of PEXEL processing as well as protein export, including impaired display of the major virulence adhesin, PfEMP1, on the erythrocyte surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target

The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

<p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p

Stable Isotopic Evidence for Methane Seeps in Neoproterozoic Postglacial Cap Carbonates

The Earth's most severe glaciations are thought to have occurred about 600 million years ago, in the late Neoproterozoic era. A puzzling feature of glacial deposits from this interval is that they are overlain by 1–5-m-thick 'cap carbonates' (particulate deep-water marine carbonate rocks) associated with a prominent negative carbon isotope excursion. Cap carbonates have been controversially ascribed to the aftermath of almost complete shutdown of the ocean ecosystems for millions of years during such ice ages—the 'snowball Earth' hypothesis. Conversely, it has also been suggested that these carbonate rocks were the result of destabilization of methane hydrates during deglaciation and concomitant flooding of continental shelves and interior basins. The most compelling criticism of the latter 'methane hydrate' hypothesis has been the apparent lack of extreme isotopic variation in cap carbonates inferred locally to be associated with methane seeps. Here we report carbon isotopic and petrographic data from a Neoproterozoic postglacial cap carbonate in south China that provide direct evidence for methane-influenced processes during deglaciation. This evidence lends strong support to the hypothesis that methane hydrate destabilization contributed to the enigmatic cap carbonate deposition and strongly negative carbon isotopic anomalies following Neoproterozoic ice ages. This explanation requires less extreme environmental disturbance than that implied by the snowball Earth hypothesis

In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1

The var-gene encoding Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is known to play a major role in the pathogenicity of the P. falciparum parasite. The protein enables the parasite to adhere to the endothelial linings of small blood vessels (cytoadherence) as well as to non-infected erythrocytes (rosetting), thus preventing clearance from the bloodstream. The development and spread of resistance towards most anti-malarial drugs used for treatment and prevention of the most severe form of malaria truly emphasise the importance of a continuous research and development of new drugs. In this study we use Systematic Evolution of Ligands by EXponential enrichment (SELEX) methodology to isolate high-affinity ligands (aptamers). To validate the results from the SELEX in vitro selection, different aptamers have been selected against PfEMP1 in a live cell assay of P. falciparum strain FCR3S1.2, a highly rosetting strain. We have been able to show the rosette disrupting capacity of these SELEX-aptamers at concentrations of 33 nM and with 100% disruption at 387 nM. The described results show that RNA aptamers are promising candidates for adjunct therapy in severe malaria

Ethnobotanical knowledge is vastly under-documented in northwestern South America

A main objective of ethnobotany is to document traditional knowledge about plants before it disappears. However, little is known about the coverage of past ethnobotanical studies and thus about how well the existing literature covers the overall traditional knowledge of different human groups. To bridge this gap, we investigated ethnobotanical data-collecting efforts across four countries (Colombia, Ecuador, Peru, Bolivia), three ecoregions (Amazon, Andes, Chocó), and several human groups (including Amerindians, mestizos, and Afro-Americans). We used palms (Arecaceae) as our model group because of their usefulness and pervasiveness in the ethnobotanical literature. We carried out a large number of field interviews (n = 2201) to determine the coverage and quality of palm ethnobotanical data in the existing ethnobotanical literature (n = 255) published over the past 60 years. In our fieldwork in 68 communities, we collected 87,886 use reports and documented 2262 different palm uses and 140 useful palm species. We demonstrate that traditional knowledge on palm uses is vastly under-documented across ecoregions, countries, and human groups. We suggest that the use of standardized data-collecting protocols in wide-ranging ethnobotanical fieldwork is a promising approach for filling critical information gaps. Our work contributes to the Aichi Biodiversity Targets and emphasizes the need for signatory nations to the Convention on Biological Diversity to respond to these information gaps. Given our findings, we hope to stimulate the formulation of clear plans to systematically document ethnobotanical knowledge in northwestern South America and elsewhere before it vanishesThis study was funded by the European Union, 7th Framework Programme (contract no. 212631), the Russel E. Train Education for Nature Program of the WWF (to NPZ), the Anne S. Chatham fellowship of the Garden Club of America (to NPZ), and the Universidad Autónoma de Madrid travel grants programme (to RCL