A sero-epidemiological approach to explore transmission of Mycobacterium ulcerans

The debilitating skin disease Buruli ulcer (BU) is caused by infection with Mycobacterium ulcerans. While various hypotheses on potential reservoirs and vectors of M. ulcerans exist, the mode of transmission has remained unclear. Epidemiological studies have indicated that children below the age of four are less exposed to the pathogen and at lower risk of developing BU than older children. In the present study we compared the age at which children begin to develop antibody responses against M. ulcerans with the age pattern of responses to other pathogens transmitted by various mechanisms. A total of 1,352 sera from individuals living in the BU endemic Offin river valley of Ghana were included in the study. While first serological responses to the mosquito transmitted malaria parasite Plasmodium falciparum and to soil transmitted Strongyloides helminths emerged around the age of one and two years, sero-conversion for M. ulcerans and for the water transmitted trematode Schistosoma mansoni occurred at around four and five years, respectively. Our data suggest that exposure to M. ulcerans intensifies strongly at the age when children start to have more intense contact with the environment, outside the small movement range of young children. Further results from our serological investigations in the Offin river valley also indicate ongoing transmission of Treponema pallidum, the causative agent of yaws

First results of the SOAP project. Open access publishing in 2010

The SOAP (Study of Open Access Publishing) project has compiled data on the present offer for open access publishing in online peer-reviewed journals. Starting from the Directory of Open Access Journals, several sources of data are considered, including inspection of journal web site and direct inquiries within the publishing industry. Several results are derived and discussed, together with their correlations: the number of open access journals and articles; their subject area; the starting date of open access journals; the size and business models of open access publishers; the licensing models; the presence of an impact factor; the uptake of hybrid open access.Comment: Submitted to PLoS ON

Highlights from the SOAP project survey. What Scientists Think about Open Access Publishing

The SOAP (Study of Open Access Publishing) project has run a large-scale survey of the attitudes of researchers on, and the experiences with, open access publishing. Around forty thousands answers were collected across disciplines and around the world, showing an overwhelming support for the idea of open access, while highlighting funding and (perceived) quality as the main barriers to publishing in open access journals. This article serves as an introduction to the survey and presents this and other highlights from a preliminary analysis of the survey responses. To allow a maximal re-use of the information collected by this survey, the data are hereby released under a CC0 waiver, so to allow libraries, publishers, funding agencies and academics to further analyse risks and opportunities, drivers and barriers, in the transition to open access publishing.Comment: Data manual available at http://bit.ly/gI8nct Compressed CSV data file available at http://bit.ly/gSmm71 Alternative data formats: CSV http://bit.ly/ejuvKO XLS http://bit.ly/e6gE7o XLSX http://bit.ly/gTjyv

Default Risk and Equity Returns: A Comparison of the Bank-Based German and the U.S. Financial System

In this paper, we address the question whether the impact of default risk on equity returns depends on the financial system firms operate in. Using an implementation of Merton's option-pricing model for the value of equity to estimate firms' default risk, we construct a factor that measures the excess return of firms with low default risk over firms with high default risk. We then compare results from asset pricing tests for the German and the U.S. stock markets. Since Germany is the prime example of a bank-based financial system, where debt is supposedly a major instrument of corporate governance, we expect that a systematic default risk effect on equity returns should be more pronounced for German rather than U.S. firms. Our evidence suggests that a higher firm default risk systematically leads to lower returns in both capital markets. This contradicts some previous results for the U.S. by Vassalou/Xing (2004), but we show that their default risk factor looses its explanatory power if one includes a default risk factor measured as a factor mimicking portfolio. It further turns out that the composition of corporate debt affects equity returns in Germany. Firms' default risk sensitivities are attenuated the more a firm depends on bank debt financing

Apolipoprotein E mediates evasion from hepatitis C virus−neutralizing antibodies

Background & Aims Efforts to develop an effective vaccine against hepatitis C virus (HCV) have been hindered by the propensity of the virus to evade host immune responses. HCV particles in serum and in cell culture associate with lipoproteins, which contribute to viral entry. Lipoprotein association has also been proposed to mediate viral evasion of the humoral immune response, though the mechanisms are poorly defined. Methods We used small interfering RNAs to reduce levels of apolipoprotein E (apoE) in cell culture−derived HCV−producing Huh7.5-derived hepatoma cells and confirmed its depletion by immunoblot analyses of purified viral particles. Before infection of naïve hepatoma cells, we exposed cell culture−derived HCV strains of different genotypes, subtypes, and variants to serum and polyclonal and monoclonal antibodies isolated from patients with chronic HCV infection. We analyzed the interaction of apoE with viral envelope glycoprotein E2 and HCV virions by immunoprecipitation. Results Through loss-of-function studies on patient-derived HCV variants of several genotypes and subtypes, we found that the HCV particle apoE allows the virus to avoid neutralization by patient-derived antibodies. Functional studies with human monoclonal antiviral antibodies showed that conformational epitopes of envelope glycoprotein E2 domains B and C were exposed after depletion of apoE. The level and conformation of virion-associated apoE affected the ability of the virus to escape neutralization by antibodies. Conclusions In cell-infection studies, we found that HCV-associated apoE helps the virus avoid neutralization by antibodies against HCV isolated from chronically infected patients. This method of immune evasion poses a challenge for the development of HCV vaccines

Compartmentalized Production of CCL17 In Vivo: Strong Inducibility in Peripheral Dendritic Cells Contrasts Selective Absence from the Spleen

Dendritic cells (DCs)* fulfill an important regulatory function at the interface of the innate and adaptive immune system. The thymus and activation-regulated chemokine (TARC/CCL17) is produced by DCs and facilitates the attraction of activated T cells. Using a fluorescence-based in vivo reporter system, we show that CCL17 expression in mice is found in activated Langerhans cells and mature DCs located in various lymphoid and nonlymphoid organs, and is up-regulated after stimulation with Toll-like receptor ligands. DCs expressing CCL17 belong to the CD11b+CD8−Dec205+ DC subset, including the myeloid-related DCs located in the subepithelial dome of Peyer's patches. CCL17-deficient mice mount diminished T cell–dependent contact hypersensitivity responses and display a deficiency in rejection of allogeneic organ transplants. In contrast to lymphoid organs located at external barriers of the skin and mucosa, CCL17 is not expressed in the spleen, even after systemic microbial challenge or after in vitro stimulation. These findings indicate that CCL17 production is a hallmark of local DC stimulation in peripheral organs but is absent from the spleen as a filter of blood-borne antigens

Causative classification of river flood events

A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches. So far no unified definition of causative mechanisms of flood events exists. Existing frameworks for classification of instrumental and preinstrumental series of flood events adopt different perspectives: hydroclimatic (large‐scale circulation patterns and atmospheric state at the time of the event), hydrological (catchment scale precipitation patterns and antecedent catchment state), and hydrograph‐based (indirectly considering generating mechanisms through their effects on hydrograph characteristics). All of these approaches intend to capture the flood generating mechanisms and are useful for characterizing the flood processes at various spatial and temporal scales. However, uncertainty analyses with respect to indicators, classification methods, and data to assess the robustness of the classification are rarely performed which limits the transferability across different geographic regions. It is argued that more rigorous testing is needed. There are opportunities for extending classification methods to include indicators of space–time dynamics of rainfall, antecedent wetness, and routing effects, which will make the classification schemes even more useful for understanding and estimating floods

Mobile Asteroid Surface Scout (MASCOT) - Design, Development and Delivery of a Small Asteroid Lander Aboard Hayabusa2

MASCOT is a small asteroid lander launched on December 3rd, 2014, aboard the Japanese HAYABUSA2 asteroid sample-return mission towards the 980 m diameter C-type near-Earth asteroid (162173) 1999 JU3. MASCOT carries four full-scale asteroid science instruments and an uprighting and relocation device within a shoebox-sized 10 kg spacecraft; a complete lander comparable in mass and volume to a medium-sized science instrument on interplanetary missions. Asteroid surface science will be obtained by: MicrOmega, a hyperspectral near- to mid-infrared soil microscope provided by IAS; MASCAM, a wide-angle Si CMOS camera with multicolour LED illumination unit; MARA, a multichannel thermal infrared surface radiometer; the magnetometer, MASMAG, provided by the Technical University of Braunschweig. Further information on the conditions at or near the lander‘s surfaces is generated as a byproduct of attitude sensors and other system sensors. MASCOT uses a highly integrated, ultra-lightweight truss-frame structure made from a CFRP-foam sandwich. It has three internal mechanisms: a preload release mechanism, to release the structural preload applied for launch across the separation mechanism interface; a separation mechanism, to realize the ejection of MASCOT from the semi-recessed stowed position within HAYABUSA2; and the mobility mechanism, for uprighting and hopping. MASCOT uses semi-passive thermal control with Multi-Layer Insulation, two heatpipes and a radiator for heat rejection during operational phases, and heaters for thermal control of the battery and the main electronics during cruise. MASCOT is powered by a primary battery during its on-asteroid operational phase, but supplied by HAYABUSA2 during cruise for check-out and calibration operations as well as thermal control. All housekeeping and scientific data is transmitted to Earth via a relay link with the HAYABUSA2 main-spacecraft, also during cruise operations. The link uses redundant omnidirectional UHF-Band transceivers and patch antennae on the lander. The MASCOT On-Board Computer is a redundant system providing data storage, instrument interfacing, command and data handling, as well as autonomous surface operation functions. Knowledge of the lander’s attitude on the asteroid is key to the success of its uprighting and hopping function. The attitude is determined by a threefold set of sensors: optical distance sensors, photo electric cells and thermal sensors. A range of experimental sensors is also carried. MASCOT was build by the German Aerospace Center, DLR, with contributions from the French space agency, CNES. The system design, science instruments, and operational concept of MASCOT will be presented, with sidenotes on the development of the mission and its integration with HAYABUSA2