298 research outputs found

    Detection and Imaging of Defects Especially Materials with Small UT Transducers Using Broad-Band Holography

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    Since conventional single frequency acoustical holography provides only poor axial resolution, this concept was improved with the multifrequency holography to enhance the imaging quality. This leads to long data acquisition times because of the need to measure each frequency. A further step towards a fast imaging system with good spatial resolution is broadband holography. Here, one illuminates the object with broadband signals in a single measurement procedure

    A breeding site model for regional, dynamical malaria simulations evaluated using in situ temporary ponds observations

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    Daily observations of potential mosquito developmental habitats in a suburb of Kumasi in central Ghana reveal a strong variability in their water persistence times, which ranged between 11 and 81 days. The persistence of the ponds was strongly tied with rainfall, location and size of the puddles. A simple power-law relationship is found to fit the relationship between the average pond depth and area well. A prognostic water balance model is derived that describes the temporal evolution of the pond area and depth, incorporating the power-law geometrical relation. Pond area increases in response to rainfall, while evaporation and infiltration act as sink terms. Based on a range of evaluation metrics, the prognostic model is judged to provide a good representation of the pond coverage evolution at most sites. Finally, we demonstrate that the prognostic equation can be generalised and equally applied to a grid-cell to derive a fractional pond coverage, and thus can be implemented in spatially distributed models for relevant vector- borne diseases such as malaria

    Mosquito breeding site water temperature observations and simulations towards improved vector-borne disease models for Africa

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    An energy budget model is developed to predict the water temperature of typical mosquito larval developmental habitats. It assumes a homogeneous mixed water column driven by empirically derived fluxes. The model shows good agreement at both hourly and daily time scales with 10-min temporal resolution observed water temperatures, monitored between June and November 2013 within a peri-urban area of Kumasi, Ghana. There was a close match between larvae development times calculated using either the model-derived or observed water temperatures. The water temperature scheme represents a significant improvement over assuming the water temperature to be equal to air temperature. The energy budget model requires observed minimum and maximum temperatures, information that is generally available from weather stations. Our results show that hourly variations in water temperature are important for the simulation of aquatic-stage development times. By contrast, we found that larval development is insensitive to sub-hourly variations. Modelling suggests that in addition to water temperature, an accurate estimation of degree-day development time is very important to correctly predict the larvae development times. The results highlight the potential of the model to predict water temperature of temporary bodies of surface water. Our study represents an important contribution towards the improvement of weather-driven dynamical disease models, including those designed for malaria early forecasting systems

    Mosquito breeding site water temperature observations and simulations towards improved vector-borne disease models for Africa

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    An energy budget model is developed to predict the water temperature of typical mosquito larval developmental habitats. It assumes a homogeneous mixed water column driven by empirically derived fluxes. The model shows good agreement at both hourly and daily time scales with 10-min temporal resolution observed water temperatures, monitored between June and November 2013 within a peri-urban area of Kumasi, Ghana. There was a close match between larvae development times calculated using either the model-derived or observed water temperatures. The water temperature scheme represents a significant improvement over assuming the water temperature to be equal to air temperature. The energy budget model requires observed minimum and maximum temperatures, information that is generally available from weather stations. Our results show that hourly variations in water temperature are important for the simulation of aquatic-stage development times. By contrast, we found that larval development is insensitive to sub-hourly variations. Modelling suggests that in addition to water temperature, an accurate estimation of degree-day development time is very important to correctly predict the larvae development times. The results highlight the potential of the model to predict water temperature of temporary bodies of surface water. Our study represents an important contribution towards the improvement of weather-driven dynamical disease models, including those designed for malaria early forecasting systems

    Short Leucine-Rich Proteoglycans Modulate Complement Activity and Increase Killing of the Respiratory Pathogen Moraxella catarrhalis

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    The respiratory pathogen Moraxella catarrhalis is a human-specific commensal that frequently causes acute otitis media in children and stimulates acute exacerbations in chronic obstructive pulmonary disease patients. The exact molecular mechanisms defining host-pathogen interactions promoting pathogenesis are not clearly understood. Limited knowledge hampers vaccine and immunotherapeutic development required to treat this emerging pathogen. In this study, we reveal in detail a novel antibacterial role displayed by short leucine-rich proteoglycans (SLRPs) in concert with complement. We show that fibromodulin (FMOD), osteoadherin (OSAD), and biglycan (BGN) but not decorin (DCN) enhance serum killing of M. catarrhalis. Our results suggest that M. catarrhalis binding to SLRPs is a conserved feature, as the overwhelming majority of clinical and laboratory strains bound all four SLRPs. Furthermore, we resolve the binding mechanism responsible for this interaction and highlight the role of the ubiquitous surface protein (Usp) A2/A2H in mediating binding to host SLRPs. A conserved immune evasive strategy used by M. catarrhalis and other pathogens is the surface acquisition of host complement inhibitors such as C4b-binding protein (C4BP). We observed that FMOD, OSAD, and BGN competitively inhibit binding of C4BP to the surface of M. catarrhalis, resulting in increased C3b/iC3b deposition, membrane attack complex (MAC) formation, and subsequently decreased bacterial survival. Furthermore, both OSAD and BGN promote enhanced neutrophil killing in vitro, both in a complement-dependent and independent fashion. In summary, our results illustrate that SLRPs, FMOD, OSAD, and BGN portray complement-modulating activity enhancing M. catarrhalis killing, defining a new antibacterial role supplied by SLRPs.</p

    Antibacterial Fusion Proteins Enhance Moraxella catarrhalis Killing

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    Moraxella catarrhalis is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed. Complement is a key component of innate immunity that mediates the detection, response, and subsequent elimination of invading pathogens. Many pathogens including M. catarrhalis have evolved complement evasion mechanisms, which include the binding of human complement inhibitors such as C4b-binding protein (C4BP) and Factor H (FH). Inhibiting C4BP and FH acquisition by M. catarrhalis may provide a novel therapeutic avenue to treat infections. To achieve this, we created two chimeric proteins that combined the Moraxella-binding domains of C4BP and FH fused to human immunoglobulin Fcs: C4BP domains 1 and 2 and FH domains 6 and 7 fused to IgM and IgG Fc, respectively. As expected, FH6-7/IgG displaced FH from the bacterial surface while simultaneously activating complement via Fc-C1q interactions, together increasing pathogen elimination. C4BP1-2/IgM also increased serum killing of the bacteria through enhanced complement deposition, but did not displace C4BP from the surface of M. catarrhalis. These Fc fusion proteins could act as anti-infective immunotherapies. Many microbes bind the complement inhibitors C4BP and FH through the same domains as M. catarrhalis, therefore these Fc fusion proteins may be promising candidates as adjunctive therapy against many different drug-resistant pathogens

    Monthly entomological inoculation rate data for studying the seasoanality of malaria transmission in Africa

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    A comprehensive literature review was conducted to create a new database of 197 field surveys of monthly malaria Entomological Inoculation Rates (EIR), a metric of malaria transmission intensity. All field studies provide data at a monthly temporal resolution and have a duration of at least one year in order to study the seasonality of the disease. For inclusion, data collection methodologies adhered to a specific standard and the location and timing of the measurements were documented. Auxiliary information on the population and hydrological setting were also included. The database includes measurements that cover West and Central Africa and the period from 1945 to 2011, and hence facilitates analysis of interannual transmission variability over broad regions

    Short Leucine-Rich Proteoglycans Modulate Complement Activity and Increase Killing of the Respiratory Pathogen Moraxella catarrhalis

    Get PDF
    The respiratory pathogen Moraxella catarrhalis is a human-specific commensal that frequently causes acute otitis media in children and stimulates acute exacerbations in chronic obstructive pulmonary disease patients. The exact molecular mechanisms defining host-pathogen interactions promoting pathogenesis are not clearly understood. Limited knowledge hampers vaccine and immunotherapeutic development required to treat this emerging pathogen. In this study, we reveal in detail a novel antibacterial role displayed by short leucine-rich proteoglycans (SLRPs) in concert with complement. We show that fibromodulin (FMOD), osteoadherin (OSAD), and biglycan (BGN) but not decorin (DCN) enhance serum killing of M. catarrhalis. Our results suggest that M. catarrhalis binding to SLRPs is a conserved feature, as the overwhelming majority of clinical and laboratory strains bound all four SLRPs. Furthermore, we resolve the binding mechanism responsible for this interaction and highlight the role of the ubiquitous surface protein (Usp) A2/A2H in mediating binding to host SLRPs. A conserved immune evasive strategy used by M. catarrhalis and other pathogens is the surface acquisition of host complement inhibitors such as C4b-binding protein (C4BP). We observed that FMOD, OSAD, and BGN competitively inhibit binding of C4BP to the surface of M. catarrhalis, resulting in increased C3b/iC3b deposition, membrane attack complex (MAC) formation, and subsequently decreased bacterial survival. Furthermore, both OSAD and BGN promote enhanced neutrophil killing in vitro, both in a complement-dependent and independent fashion. In summary, our results illustrate that SLRPs, FMOD, OSAD, and BGN portray complement-modulating activity enhancing M. catarrhalis killing, defining a new antibacterial role supplied by SLRPs

    Seasonality of Plasmodium falciparum transmission: a systematic review

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    This article is fully open access and the published version is available free of charge from the jounal website.http://www.malariajournal.com/content/14/1/343Background Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has “strongly seasonal” transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized. Methods The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts. Results and discussion 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both). Discussion Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location. Conclusions The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales. Keywords: Plasmodium falciparum ; Seasonality; Climatic driversAcknowledgements This work was supported by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, and Fogarty International Center, National Institutes of Health. DLS is funded by a grant from the Bill & Melinda Gates Foundation (OPP1110495), which also supports RCR. PMA is grateful to the University of Utrecht for supporting him with The Belle van Zuylen Chair. PWG is a Career Development Fellow (K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and receives support from the Bill and Melinda Gates Foundation (OPP1068048, OPP1106023)
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